Pesticidal compositions and processes related thereto

ABSTRACT

This document discloses molecules having the following formula (“Formula One”): 
     
       
         
         
             
             
         
       
     
     and processes associated therewith.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/739,025 filed Dec. 19, 2012, the disclosure of which is expressly incorporated herein by reference.

FIELD OF THE DISCLOSURE

The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.

BACKGROUND OF THE DISCLOSURE

Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.

Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pesticides, for example, imidacloprid.

Therefore, for many reasons, including the above reasons, a need exists for new pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.

“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

“Alkoxy” means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.

“Alkyl” means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C₃)alkyl which represents n-propyl and isopropyl), (C₄)alkyl which represents n-butyl, sec-butyl, isobutyl, and tert-butyl.

“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.

“Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

“(C_(x)-C_(y))” where the subscripts “x” and “y” are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent—for example, (C₁-C₄)alkyl means methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl, each individually.

“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at least one carbon-carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.

“Cycloalkenyloxy” means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.

“Halo” means fluoro, chloro, bromo, and iodo.

“Haloalkoxy” means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

“Haloalkyl” means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

“Heterocyclyl” means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl.

Additional examples include the following

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules having the following formula (“Formula One”):

wherein:

(a) R1 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(b) R2 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(c) R3 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(d) R4 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(e) R5 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(f) R6 is a (C₁-C₈)haloalkyl;

(g) R7 is selected from H, F, Cl, Br, I, OH, (C₁-C₈)alkoxy, and halo(C₁-C₈)alkoxy;

(h) R8 is selected from H, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, OR14, and N(R14)(R15);

(i) R9 is selected from H, F, Cl, Br, I, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, OR14, and N(R14)(R15);

(j) R10 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl,         S(O)(halo(C₁-C₈)alkyl), S(O)₂(C₁-C₈)alkyl,         S(O)₂(halo(C₁-C₈)alkyl), NR14R15, C(═O)H, C(═O)N(R14)(R15),         CN(R14)(R15)(═NOH), (C═O)O(C₁-C₈)alkyl, (C═O)OH, heterocyclyl,         (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl,     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from OH,         (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,         S(O)₂(C₁-C₈)alkyl, NR14R15, and     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from         (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,         S(O)₂(C₁-C₈)alkyl, and N(R14)(R15);

(k) R11 is selected from C(═X5)N(R14)₄C₁-C₈)alkylC(═X5)N(R14)(R15)) wherein each X5 is independently selected from O, or S;

(l) R12 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, and cyclo(C₃-C₆)alkyl;

(m) R13 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, and halo(C₁-C₈)alkoxy;

(n) each R14 is independently selected from H, (C₁-C₈)alkyl, (C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted halo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),         N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently         selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,         and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be         further substituted with one or more of F, Cl, Br, I, CN, and         NO₂);

(o) each R15 is independently selected from H, (C₁-C₈)alkyl, (C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted halo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),         N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently         selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,         and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be         further substituted with one or more of F, Cl, Br, I, CN, and         NO₂);

(p) each R16 is independently selected from H, (C₁-C₈)alkyl, substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo;

(q) each R17 is independently selected from H, (C₁-C₈)alkyl, substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo;

(r) X1 is selected from N and CR12;

(s) X2 is selected from N, CR9, and CR13;

(t) X3 is selected from N and CR9; and

(v) R12 and R13 together form a linkage containing 3 to 4 atoms selected from C, N, O, and S, wherein said linkage connects back to the ring to form a 5 to 6 member saturated or unsaturated cyclic ring, wherein said linkage has at least one substituent X4 wherein X4 is selected from R14, N(R14)(R15), N(R14)(C(═O)R14), N(R14)(C(═S)R14), N(R14)(C(═O)N(R14)(R14)), N(R14)(C(═S)N(R14)(R14)), N(R14)(C(═O)N(R14)((C₂-C₈)alkenyl)), N(R14)(C(═S)N(R14)((C₂-C₈)alkenyl)), wherein each R14 is independently selected.

In another embodiment of this invention R1 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R2 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R3 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R4 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R5 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R2 and R4 are selected from F, Cl, Br, I, CN, and NO₂ and R1, R3, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are selected from F, Cl, Br, I, CN, and NO₂ and R1, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are independently selected from F and Cl and R1 and R5 are H.

In another embodiment of this invention R1 is selected from Cl and H.

In another embodiment of this invention R2 is selected from CF₃, CH₃, Cl, F, and H.

In another embodiment of this invention R3 is selected from OCH₃, CH₃, F, Cl, or H.

In another embodiment of this invention R4 is selected from CF₃, CH₃, Cl, F, and H.

In another embodiment of this invention R5 is selected from F, Cl, and H.

In another embodiment of this invention R6 may be selected from any combination of one or more of the following—halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R6 is trifluoromethyl.

In another embodiment of this invention R7 may be selected from any combination of one or more of the following —H, F, Cl, Br, and I.

In another embodiment of this invention R7 is selected from H, OCH₃, and OH.

In another embodiment of this invention R8 may be selected from any combination of one or more of the following —H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R8 is selected from CH₃ and H.

In another embodiment of this invention R9 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R10 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, CN, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, halo(C₈)alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In another embodiment of this invention R10 may be selected from any combination of one or more of the following —H, Cl, Br, CH₃, and CF₃.

In another embodiment of this invention R10 is selected from Br, C(═NOH)NH₂, C(═O)H, C(═O)NH₂, C(═O)OCH₂CH₃, C(═O)OH, CF₃, CH₂CH₃, CH₂OH, CH₃, Cl, CN, F, H, NH₂, NHC(═O)H, NHCH₃, NO₂, OCH₃, OCHF₂, and pyridyl.

In another embodiment of this invention R11 may be selected from any combination of one or more of the following —C(═O)N(H)(C((CH₃)₂)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₂CH₃)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═S)N(H)(CH₂CF₃)), C(═O)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)), and C(═S)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)).

In another embodiment of this invention R11 is C(═(O or S))N(H)(((C₁-C₈)alkyl)C(═(O or S))N(H)(halo(C₁-C₈)alkyl)), which may be used in combination with any embodiment of R1 through R10 and X1 through X3.

In another embodiment of this invention R12 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R12 is selected from CH3, and H.

In another embodiment of this invention R13 may be selected from any combination of one or more of the following —H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R13 is selected from CH₃, Cl and H.

In another embodiment of this invention R12-R13 are a hydrocarbyl linkage containing CH═CHCH═CH.

In another embodiment of this invention R14 may be selected from any combination of one or more of the following —H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17), ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17), (C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17), (C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and (C₈)alkyl-C(═O)N(R16)(R17).

In another embodiment of this invention R14 may be selected from any combination of one or more of the following —H, CH₃, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl, N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃).

In another embodiment of this invention R15 may be selected from any combination of one or more of the following —H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17), ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17), (C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17), (C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and (C₈)alkyl-C(═O)N(R16)(R17).

In another embodiment of this invention R15 may be selected from any combination of one or more of the following —H, CH₃, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl, N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃).

In another embodiment of this invention R16 may be selected from any combination of one or more of the following —H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), and O—(C₈)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R16 may be selected from any combination of one or more of the following —H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl.

In another embodiment of this invention R17 may be selected from any combination of one or more of the following —H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), and O—(C₈)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R17 may be selected from any combination of one or more of the following —H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl.

In another embodiment of this invention X1 is CR12, X2 is CR13, and X3 is CR9.

In another embodiment of this invention a heterocyclyl has preferably about 6 to 10 atoms in the ring structure, more preferably, 6 to 8 atoms.

The molecules of Formula One will generally have a molecular mass of about 100 Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally preferred if the molecular mass is from about 140 Daltons to about 600 Daltons.

The benzyl alcohol of Formula IV, wherein R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, can be synthesized in two ways. One way, disclosed in step a of Scheme I, is by treatment of the ketone of Formula II, wherein R1, R2, R3, R4, R5, and R6 are as previously disclosed, with a reducing agent, such as sodium borohydride (NaBH₄), under basic conditions, such as aqueous sodium hydroxide (NaOH), in a polar protic solvent, such as methyl alcohol (MeOH) at 0° C. Alternatively, an aldehyde of Formula III, wherein R1, R2, R3, R4, R5, and R7 are as previously disclosed, is allowed to react with trifluorotrimethylsilane in the presence of a catalytic amount of tetrabutylammonium fluoride (TBAF) in a polar aprotic solvent, such as tetrahydrofuran (THF), as in step b of Scheme I. The compound of Formula IV can be transformed into the compound of Formula V, wherein Y is selected from Br, Cl or I, and R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, by reaction with a halogenating reagent, such as N-bromosuccinimide (NBS) and triethyl phosphite in a non-reactive solvent, such as dichloromethane (CH₂Cl₂) at reflux temperature to provide Y═Br, or such as thionyl chloride and pyridine in a hydrocarbon solvent, such as toluene at reflux temperature to provide Y═Cl, as in step c of Scheme I.

Formation of the styrene coupling partners can be accomplished as in Schemes II, III IV and V.

In Scheme II, a vinylbenzoic acid of Formula VI, wherein R11 is (C═O)OH and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, can be converted in two steps to the vinylbenzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, and X are as previously disclosed. As in step d of Scheme II, the benzoic acid of Formula VI is treated with oxalyl chloride in the presence of a catalytic amount of N,N-dimethylformamide (DMF) in a non-reactive solvent such as CH₂Cl₂ to form the acid chloride, which is subsequently allowed to react with an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, in the presence of a base, such as triethylamine (TEA), in a polar aprotic solvent, such as THF, to provide the vinyl benzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, as in step e of Scheme II.

In Schemes III and IV, a halobenzoic acid of Formula VIII, wherein R18 is Br or I, R11 is (C═O)OH and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed can be converted to a vinylbenzoic acid ester of Formula VIIb1 or Formula VIIb2, wherein R18 is Br or I, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. In step f of Scheme III, the halobenzoic acid of Formula VIII, wherein R18 is Br, is treated with a base, such as n-butyllithium (n-BuLi), and DMF in a polar, aprotic solvent, such as THF, at a temperature of about −78° C. The resulting formyl benzoic acid is allowed to react with an acid, such as sulfuric acid (H₂SO₄), in the presence of an alcohol, such as ethyl alcohol (EtOH), as in step g, to provide the formyl benzoic acid ethyl ester of Formula IX, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The vinyl benzoic acid ester of Formula VIIb1 is accessed via reaction of the compounds of Formula IX, with a base, such as potassium carbonate (K₂CO₃), and methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, at ambient temperature, as in step h of Scheme III.

In step i of Scheme IV, the halobenzoic acid of Formula VIII, wherein R18 is Br, R11 is (C═O)OH, and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, is treated with di-tert-butyl dicarbonate in the presence of a base, such as TEA and a catalytic amount of 4-(dimethylamino)pyridine (DMAP) in a polar aprotic solvent, such as THF, at ambient temperature. The resulting benzoic acid tert-butyl ester is allowed to react with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such a tetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄), and a base, such as K₂CO₃, in a non-reactive solvent such as toluene at reflux temperature, as in step j, to provide the vinyl benzoic acid ester of Formula VIIb2, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In step k of Scheme V, the vinyl benzoic acid ester of Formula VIIb2, wherein R10 is Br, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1, X2, and X3 are as previously defined, can be further transformed into the corresponding vinyl benzoic acid ester of Formula VIIb3, wherein R10 is CN, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with copper(I) cyanide (CuCN) in a polar aprotic solvent, such as DMF, at 140° C.

Coupling of the compounds of Formula V with the compounds of Formula VIIa, VIIb1, VIIb2 and VIIb3 can be accomplished as in Schemes VI, VII, and VIII. In step l of Scheme VI, a compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of copper(I) chloride (CuCl) and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula VIIb1, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the compounds of Formula Xa, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula Xa are then converted to the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, by either a two-step process as disclosed in steps m and n or in one step as disclosed in step o. In step m of Scheme VII, the ester of Formula Xa is saponified to the corresponding acid under acidic conditions, such as about 11 Normal (N) hydrochloric acid (HCl), in a polar aprotic solvent, such as 1,4-dioxane, at about 100° C. The acid can subsequently be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed using peptide coupling reagents, such as 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC.HCl), benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP), 1-hydroxy-7-azabenzotriazole (HOAt), or O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate (HBTU) in the presence of a base, such as N,N-diisopropylethylamine (DIPEA) or DMAP to give the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed. Alternatively, the ester of Formula Xa is allowed to react with an amine (HN(R14)(R15)) in the presence of a solution of trimethylaluminum in toluene in a non-reactive solvent, such as CH₂Cl₂, at ambient temperature, as in step o of Scheme VII, to access the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VIII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula VIIb2 or VIIb3, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the compounds of Formula Xb, wherein R11 is (C═O)OH, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed. The compounds of Formula Xb are then converted to the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, in one step as disclosed in step n. In step n of Scheme VIII, the acid of Formula Xb can be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, using peptide coupling reagents, such as HOBt, EDC.HCl, PyBOP, CIP, HOAt, or HBTU in the presence of a base, such as DIPEA or DMAP to give the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step t of Scheme XIII, the vinyl benzyl chloride of Formula XIa, wherein R11 is —CH₂Cl and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be transformed into the corresponding phthalimide-protected benzyl amine of Formula XIIa, wherein R11 is CH₂N(Phthalimide), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 70° C.

In step u of Scheme XIV, the 4-methylbenzonitrile of Formula XIIIa, wherein R11 is CH₃ and R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be transformed into the corresponding benzyl bromide of Formula XIVa, wherein R11 is CH₂Br and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with NBS and azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as carbon tetrachloride (CCl₄) at 77° C. The nitrile group (CN) of Formula XIVa can be reduced to the corresponding aldehyde of Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13, X1, X2, and X3 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0° C., followed by quenching with 1.0 M HCl as in step v of Scheme XIV. The compound of Formula XVa can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIa, wherein R11 is CH₂N(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60° C. as in step t of Scheme XIV. In step w of Scheme XIV, the aldehyde of Formula XVIa can be converted to the olefin of Formula XIIb, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CO₃, at ambient temperature.

The aldehyde of Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be reacted with a nucleophile, such as 2-aminopyridine, in a polar aprotic solvent, such as N,N-dimethylacetamide (DMA), in the presence of a base, such as K₂CO₃, at ambient temperature to provide the compound of Formula XVII, wherein R11 is CH₂NH(2-pyridine) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, as in step x of Scheme XV. In step w of Scheme XV, the compound of Formula XVII can be converted to the olefin of Formula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In a two-step, one-pot reaction as in steps y and z of Scheme XVI, the compound of Formula XIX can be reacted with the compounds of Formula XX, wherein R10 and R11 are C₁, X1 is N, and R9, R13, X2, and X3 are as previously disclosed, in the presence of a base, such as sodium hydride (NaH), and a polar aprotic solvent, such as DMF, at ambient temperature to provide the compounds of Formula XXI, wherein R10 is Cl, R11 is (CH)NH₂CO₂CH₂CH₃, X1 is N, and R9, R13, X2, and X3 are as previously defined. Hydrolysis and decarboxylation of the compounds of Formula XXI can be accomplished by reaction under acidic conditions, such as with 3 N HCl, at reflux temperature, to afford the compounds of Formula XXII, wherein R10 is Cl, R11 is CH₂NH₂.HCl, X1 is N, and R9, R13, X2, and X3 are as previously disclosed, as in step aa in Scheme XVI. The compounds of Formula XXII can be further transformed to the corresponding phthalimide-protected benzyl amines of Formula XXIIIa, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R9, R13, X1, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in the presence of a base, such as TEA, and an aprotic solvent, such as toluene, at reflux temperature as in step ab of Scheme XVI. The bromide of Formula XXIIIa can be converted to the olefin of Formula XIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R8, R9, R13, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a non-reactive solvent such as toluene at reflux temperature, as in step ac of Scheme XVI.

In step u of Scheme XVII, the 4-methylnaphthonitrile of Formula XIIIb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₃, and R12, R13, X1 and X2 are as previously defined, can be transformed into the corresponding naphthyl bromide of Formula XIVb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂Br, and R12, R13, X1 and X2 are as previously disclosed, by reaction with NBS and AIBN in a non-reactive solvent, such as CCl₄ at 77° C. The nitrile group (CN) of Formula XIVb can be reduced to the corresponding aldehyde of Formula XVb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non-aromatic ring), R11 is CH₂Br, and R12, R13, X1 and X2 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0° C., followed by quenching with 1.0 M HCl as in step v of Scheme XVII. The compound of Formula XVb can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide), and R12, R13, X1 and X2 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60° C. as in step t of Scheme XVII. In step w of Scheme XVII, the aldehyde of Formula XVIb can be converted to the olefin of Formula XIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide), and R8, R12, R13, X1 and X2 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CO₃, at ambient temperature.

The compound of Formula XXIV, wherein R11 is NHNH₂.HCl and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, can be transformed into the corresponding phthalimide-protected hydrazine of Formula XXV, wherein R11 is NHN(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in glacial acetic acid (AcOH) at reflux temperature as in step ad of Scheme XVIII. The bromide of Formula XXV can be converted to the olefin of Formula XIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R10, R13, X1, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a polar aprotic solvent such as 1,2-dimethoxyethane at 150° C. under microwave conditions, as in step ae of Scheme XVIII.

In step of Scheme XIX, the compound of Formula XXVI, wherein R11 is B(OH)₂, and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react with 2-hydroxyisoindoline-1,3-dione in the presence of CuCl and pyridine in a solvent, such as 1,2-dichlorobenzene, at ambient temperature to provide the compound of Formula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In step l of Scheme XX, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIa, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIa, wherein R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIa is removed as in step ag of Scheme XX by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIa, wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIa can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by acylation with an anhydride, such as acetic anhydride, and a base, such as TEA, in a non-reactive solvent such as CH₂Cl₂ at 0° C. as in step ah₁ of Scheme XX.

In step l of Scheme XXI, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIb, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIb, wherein R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIb is removed as in step ag of Scheme XXI by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIb, wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as DMF, as in step ak_(2a) of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═S)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a thioacid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as DMF, as in step ah₂ of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, in two steps. The first step (step ah_(3a) of Scheme XXI) involves reaction with an aldehyde in a polar protic solvent such as MeOH, followed by reaction with NaBH₄. The second step (step ah_(3b) of Scheme XXI) involves acylation with an acid chloride, such as cyclopropylcarbonyl chloride, and a base, such as TEA, in a non-reactive solvent such as CH₂Cl₂ at ambient temperature of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an isocyanate (step ai₁ of Scheme XXI) or a carbamoyl chloride (step ai₂ of Scheme XXI) in the presence of a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at 0° C.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═S)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an isothiocyanate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at 0° C., as in steps aj of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a dicarbonate, such as di-tert-butyl dicarbonate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at ambient temperature, as in steps ak of Scheme XXI.

In yet another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a chlorooxalic acid ester, such as 2-chloro-2-oxoacetate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at 0° C., as in steps al of Scheme XXI.

In step l of Scheme XXII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R8, R9, R12, R13, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIc is removed as in step ag of Scheme XXII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIc, wherein R10 is Cl, R11 is CH₂NH₂, X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIc can be transformed into the compounds of Formula One, wherein R10 is Cl, R11 is CH₂N(C═O)(R14), X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXII.

In step l of Scheme XXIII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non-aromatic ring), R11 is CH₂N(Phthalimide) and R8, R9, R12, R13, X1 and X2 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIId is removed as in step ag of Scheme XXIII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed. The compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIII.

In another embodiment, the compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1 and X2 are as previously disclosed, by reaction with an isocyanate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂Cl₂ at 0° C. as in step ai₁ of Scheme XXIII.

In step l of Scheme XXIV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIe, wherein R11 is NHN(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIe is removed as in step ag of Scheme XXIV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIe, wherein R11 is NHNH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIe can be transformed into the compounds of Formula One, wherein R11 is NHN(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIV.

In step l of Scheme XXV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIf, wherein R11 is ON(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIf is removed as in step ag of Scheme XXV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIf, wherein R11 is ONH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIf can be transformed into the compounds of Formula One, wherein R11 is ON(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXV.

In step l of Scheme XXVI, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula One, wherein R11 is CH₂NH(2-pyridine), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

The compounds of Formula One can be further elaborated by standard methods. For example, when R11 contains a thioether, the thioether can be oxidized to the sulfone by treatment with oxone in the presence of an acetone:water mixture at ambient temperature. When R11 contains an oxalate ester, the compound of Formula One can be transformed into the corresponding oxalamide by reaction with an amine hydrochloride and a solution of trimethylaluminum in toluene in a non-reactive solvent such as CH₂Cl₂.

In Scheme XXVII, a fluorobenzaldehyde of Formula XXIX, wherein R10, X1, X2, and X3 are as previously disclosed can be converted to a (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R10, X1, X2, and X3 are as previously disclosed by reaction with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as K₂CO₃, in a solvent such as DMF as in step aj. In step ak, the (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX is converted to a (1,2,4-triazol-1-yl)vinyl benzene of Formula XXXIa wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1, X2, and X3 are as previously disclosed by reaction with triphenyl phosphonium bromide in the presence of a base, such as K₂CO₃, in an aprotic solvent, such as 1,4-dioxane.

In Scheme XXVIII, a bromofluorobenzene of Formula XXXII, wherein R10, X1, X2, and X3 are as previously disclosed can be converted to a (1,2,4-triazol-1-yl)vinylbenzene of Formula XXXIb, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1, X2, and X3 are as previously disclosed in two steps. In step al, the bromofluorobenzene is reacted with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as K₂CO₃, in a solvent such as DMF to generate the (1,2,4-triazol-1-yl)bromobenzene. In step c/, the (1,2,4-triazol-1-yl)bromobenzene is reacted with vinyl boronic anhydride pyridine complex in the presence of a catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃ in a solvent such as toluene.

Coupling of the compounds of Formula V with compounds of Formula XXXIa and XXXIb can be accomplished as in Schemes XXIX. In step l, a compound of Formula V, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and a vinylbenzene of Formula XXXIa or XXXIb, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R9, R10, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the molecules of Formula One, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed.

In Scheme XXX, compounds of Formula XXXIII wherein R11 is a 3-nitro-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed can be converted to compounds of Formula One, wherein R11 is a 3-amido-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed by a two-step process. In step am, the 3-nitro-1,2,4-triazol-1-yl group is reduced to a 3-amino-1,2,4-triazol-1-yl group in the presence of zinc dust and ammonium chloride (NH₄Cl) in a protic solvent, such as MeOH. In step an, the 3-amino-1,2,4-triazol-1-yl group is acylated with an acid chloride, such as cyclopropylcarbonyl chloride or acetyl chloride, in the presence of a base, such as TEA, in a solvent such as CH₂Cl₂.

In step ao of Scheme XXXI, a bromophenyl methyl ketone of Formula XXXIV wherein R10, X1, X2, and X3 are as previously disclosed is converted to an phenyl methyl ketone of the Formula XXXV wherein R11 is a 1,2,4-triazol-1-yl group, and R10, X1, X2, and X3 are as previously disclosed by treatment with 1,2,4-triazole in the presence of a base, such as cesium carbonate (Cs₂CO₃), and a catalyst, such as copper iodide (CuI), in a solvent, such as DMF. In step ap, the 1,2,4-triazolylacetophenone of Formula XXXV is converted to the trimethylsilyl enol ether of Formula XXXVI by treatment with trimethylsilyl triflluoromethanesulfonate in the presence of a base, such as TEA, in an aprotic solvent, such as CH₂Cl₂. In step aq, the silyl enol ether is reacted with a compound of Formula V, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene at a temperature of about 180° C. to generate a ketone of the Formula XXXVII, wherein R11 is a 1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previously disclosed. In step ar, the ketone of the Formula XXXVII is treated with methylmagnesium bromide in an aprotic solvent, such as THF to generate the tertiary alcohol. The tertiary alcohol then undergoes an elimination reaction when treated with a catalytic amount of p-toluenesulfonic acid in a solvent, such as toluene, when heated to a temperature to allow azeotropic removal of water to produce compounds of Formula One wherein R11 is a 1,2,4-triazol-1-yl group, R8 is methyl, and R1, R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previously disclosed, as in step as.

In Scheme XXXII, a compound of Formula XXXVIII, wherein R10 and R11 together form a linkage, having 3-4 carbon atoms and an oxo substituent and with the ring carbon atoms form a 5- or 6-membered cyclic ring, and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula One, wherein R10 and R11 together form a linkage, having 3-4 carbon atoms and an alkylamine substituent with the ring carbon atoms form a 5- or 6-membered cyclic ring and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, by treatment with an alkylamine, such as 3,3,3-trifluoropropylamine, in the presence of a reducing agent, such as sodium cyanoborohydride (NaBH₃CN), in a solvent, such as 1,2-dichloroethane (DCE).

In Scheme XXXIII, a compound of Formula XXXIX, wherein X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XL, wherein X1, X2, and X3 are as previously disclosed, by treatment with a reducing agent, such as NaBH₃CN, in a solvent, such as AcOH, as in step au. In step av, the nitrogen atom is protected with a tert-butyloxycarbonyl (BOC) group by reaction with di-tert-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as acetonitrile (MeCN). The bromide of Formula XL can be converted to the olefin of Formula XLI, wherein R8, X1, X2 and X3 are as previously disclosed, by reaction with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂(dppf), and a base, such as K₂CO₃, in a polar aprotic solvent such as dimethylsulfoxide (DMSO) at 100° C., as in step aw.

In Scheme XXXIV, a compound of Formula XXXIX, wherein X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLII, wherein X1, X2, and X3 are as previously disclosed in two steps. In step ax, the olefin is formed by treatment of the bromide with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂, and a ligand, such as triphenylphosphine, and a base, such as Cs₂CO₃, in a solvent mixture such as THF/water. In step ay, the nitrogen atom is protected with a BOC group by reaction with di-tert-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as MeCN.

In step l of Scheme XXXV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XLI or XLII, wherein R8, X1, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 150° C. to provide the corresponding compounds of Formula XLIIIa or XLIIIb, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed.

In Scheme XXXVI, a compound of Formula XLIIIa, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLIV, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed by treatment with trifluoroacetic acid (TFA), in a solvent such as CH₂Cl₂, as in step az. Compounds of the Formula XLIV can then be transformed into compounds of the Formula XLV wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, in two steps. In step ba, the indoline is treated with sodium nitrite (NaNO₂), in an acid, such as concentrated HCl, at a temperature around 5° C., to form the nitrosoindole. In step bb, the nitrosoindole is reacted with NH₄Cl in the presence of zinc powder in a protic solvent, such as MeOH. In step bc, compounds of the Formula XLV are transformed into compounds of the Formula XLVI, wherein X4 is N(R14)(C(═O)R14) and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, by treatment with and acid, such as 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂.

In Scheme XXXVII, a compound of Formula XLIIIb, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is converted to an indole of Formula XLVII, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed by treatment with TFA, in a solvent such as CH₂Cl₂, as in step bd. Compounds of the Formula XLVII can be transformed into compounds of the Formula XLVIII wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, by reaction with 4-nitrophenyl-2-((tert-butoxycarbonyl)amino)acetate in the presence of potassium fluoride (KF) and a crown ether, such as 18-crown-6-ether, in a solvent, such as MeCN, as in step be. Compounds of the Formula XLVIII can be transformed into compounds of the Formula XLIX, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed in two steps. In step bf, the Boc group is removed by treatment with TFA, in a solvent such as CH₂Cl₂. In step bg, the amine is treated with 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂.

In Scheme XXXVIII, a compound of Formula L, wherein X1, X2, and X3 are as previously disclosed is converted to a compound of the Formula LI, wherein X1, X2, and X3 are as previously disclosed by treatment with copper (II) sulfate pentahydrate and Zn powder in a base, such as NaOH as in step bh. Compounds of the Formula LI can be transformed into compounds of the Formula LII wherein X1, X2, and X3 are as previously disclosed, by reaction with hydrazine, in a solvent such as water, at a temperature around 95° C., as in step bi. In step bj, the olefin of the Formula LIII wherein X1, X2, and X3 are as previously disclosed is formed by treatment of the bromide with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂(dppf), and a base, such as K₂CO₃, in a solvent mixture such as DMSO. Compounds of the Formula LIV, wherein X1, X2, and X3 are as previously disclosed, can be formed from compounds of the Formula LIII by reaction with ethyl bromoacetate, in the presence of a base, such as Cs₂CO₃, in a solvent, such as DMF.

In step l of Scheme XXXIX, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compound of Formula LIV, wherein R8, X1, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compound of Formula LV, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed. The compound of Formula LV can be further transformed into a compound of the Formula LVI, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, in two steps. In step bl, the ester is hydrolyzed to the acid in the presence of HCl and AcOH, at a temperature of about 100° C. In step bm, the acid is treated with an amine, such as 2,2,2-trifluoroethylamine, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂.

In step bn of Scheme XL, carboxylic acids of the Formula LVII, wherein R11 is C(═O)OH and R8, R10, X1, X2, and X3 are as previously disclosed and compounds of the Formula V, wherein Y is Br and R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as N-methyl pyrrolidine, at a temperature of about 150° C. to afford compounds of Formula LVIII, wherein R11 is (C═O)OH and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previously disclosed. Compounds of the Formula LVIII can be further transformed to the corresponding benzamides of Formula LIX, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previously disclosed, by treatment with an amine, such as 2-amino-N-(2,2,2-trifluoroethyl)acetamide, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step bo.

EXAMPLES

The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw, or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. ¹H NMR spectral data are in ppm (δ) and were recorded at 300, 400, or 600 MHz, and ¹³C NMR spectral data are in ppm (δ) and were recorded at 75, 100, or 150 MHz, unless otherwise stated.

Example 1 Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

Step 1 Method A. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (procured from Rieke Metals, UK; 5.0 grams (g), 20.5 millimoles (mmol)) in MeOH (100 milliliters (mL)) at 0° C. were added NaBH₄ (3.33 g, 92.5 mL) and 1 N aqueous NaOH solution (10 mL). The reaction mixture was warmed to 25° C. and stirred for 2 hours (h). After the reaction was deemed complete by thin layer chromatography (TLC), saturated aqueous NH₄Cl solution was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was diluted with diethyl ether (Et₂O) and washed with water (3×50 mL). The organic layer was dried over sodium sulfate (Na₂SO₄) and concentrated under reduced pressure to afford the title compound as a liquid (4.0 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 3H), 5.00 (m, 2H), 2.74 (s, 1H); ESIMS m/z 242.97 ([M−H]⁻). Step 1 Method B. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI12)

To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57 mmol) in THF (250 mL) were added trifluoromethyltrimethylsilane (9.79 g, 69.2 mmol) and a catalytic amount of TBAF. The reaction mixture was stirred at 25° C. for 8 h. After the reaction was deemed complete by TLC, the reaction mixture was diluted with 3 N HCl and then was stirred for 16 h. The reaction mixture was diluted with water and was extracted with ethyl acetate (EtOAc; 3×). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a liquid (8.41 g, 60%).

The following compounds were made in accordance with the procedures disclosed in Step 1 Method A of Example 1 above.

2,6-Difluoro-4-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile

The product was isolated as a brown solid: mp 83-87° C.; ¹H NMR (300 MHz, CDCl₃) δ 7.26 (d, J=9.0 Hz, 2H), 5.12 (d, J=6.0 Hz, 1H), 3.06 (s, 1H); ESIMS m/z 237.1 ([M+H]⁺).

1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanol

The product was isolated as a pale yellow liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.06 (d, J=8.4 Hz, 2H), 4.97-4.94 (m, 1H), 4.03 (s, 3H), 2.64 (s, 1H); EIMS m/z 242.1 ([M]⁺); IR (thinfilm) 3459, 1135 cm⁻¹.

1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-ol

The product was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.65-7.62 (m, 2H), 7.41 (d, J=8.4 Hz, 1H), 6.49 (d, J=5.1 Hz, 1H), 4.87-4.78 (m, 1H), 1.53 (t, J=18.9 Hz, 3H); EIMS m/z 240.0 ([M]⁺); IR (thinfilm) 3434, 1131, 801, 512 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Step 1 Method B of Example 1 above.

2,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethanol (AI3)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z 278 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (AI4)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z 262 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (AI5)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.60 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H), 2.60 (s, 1H); EIMS m/z 244 ([M]⁺).

1-(3,5-Dibromophenyl)-2,2,2-trifluoroethanol

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.67 (s, 1H), 7.58 (s, 2H), 5.08-5.02 (m, 1H), 4.42 (bs, 1H); EIMS m/z 333.7 ([M]⁺); IR (thin film) 3417, 2966, 1128, 531 cm⁻¹.

2,2,2-Trifluoro-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethanol

The title molecule was isolated as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.56 (s, 1H), 7.45-7.37 (m, 2H), 5.11 (q, J=6.4 Hz, 1H), 3.22 (bs, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 162.42 (d, J=249.5 Hz), 137.46 (d, J=7.8 Hz), 132.89 (qd, J=33.5, 7.9 Hz), 123.67 (q, J=283.8 Hz), 122.92 (q, J=270.68 Hz), 120.10 (t, J=4.1 Hz), 118.13 (d, J=23.0 Hz), 113.94 (dq, J=24.2, 3.9 Hz), 71.57 (q, J=32.4 Hz); EIMS m/z 262 ([M]⁺).

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol

The product was isolated as a white solid (4.98 g, 77%): mp 42-46° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.83-7.50 (m, 3H), 5.10 (p, J=6.2 Hz, 1H), 2.88 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 137.12, 135.84, 131.4, 133.03 (q, J=33.3 Hz), 127.15 (q, J=3.8 Hz), 124.50 (q, J=308.0 Hz), 123.45 (q, J=301.8 Hz), 123.04, 72.06 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.93, −78.43; EIMS m/z 278 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanol

The product was isolated as a brown liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=6.8 Hz, 1H), 7.69-7.67 (m, 1H), 7.28-7.23 (m, 1H), 5.05-5.02 (m, 1H); ESIMS m/z 261.1 ([M−H]⁻); IR (thin film) 3418, 1131 cm⁻¹.

2,2,2-Trifluoro-1-(3,4,5-trifluorophenyl)ethanol

The product was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.19-7.10 (m, 2H), 5.03-4.96 (m, 1H), 2.85 (bs, 1H); EIMS m/z 230.1 ([M]⁺).

2,2,2-Trifluoro-1-(2,3,4-trifluorophenyl)ethanol

The product was isolated as a clear colorless liquid (4.61 g 66%): ¹H NMR (400 MHz, CDCl₃) δ 7.23 (qd, J=7.4, 6.1, 4.2 Hz, 1H), 6.93 (tdd, J=9.2, 6.9, 2.2 Hz, 1H), 5.25 (q, J=6.3 Hz, 1H), 3.02-2.74 (m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 151.79 (ddd, J=254.5, 9.8, 3.4 Hz), 149.52 (ddd, J=253.5, 11.0, 3.5 Hz), 139.67 (dt, J=252.5, 15.3 Hz), 123.68 (q, J=282.2 Hz), 122.48 (dt, J=8.2, 4.1 Hz), 118.95 (dd, J=10.6, 3.6 Hz), 112.73 (dd, J=17.7, 3.9 Hz), 66.58-64.42 (m); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.95 (d, J=6.2 Hz), −132.02 (dd, J=20.0, 8.2 Hz), −137.89 (m), 159.84 (t, J=20.3 Hz); EIMS m/z 230 ([M]⁺).

2,2,2-Trifluoro-1-(2,4,5-trichlorophenyl)ethanol

The product was isolated as a white solid (3.37 g, 73%): mp 70-73° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.63 (d, J=2.5 Hz, 1H), 7.54 (d, J=2.5 Hz, 1H), 5.72-5.57 (m, 1H), 2.85 (d, J=4.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −77.84.

1-(4-Chloro-3-nitrophenyl)-2,2,2-trifluoroethanol

The product was isolated as a yellow oil (6.52 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 8.04 (d, J=2.0 Hz, 1H), 7.75-7.51 (m, 2H), 5.16 (m, 1H), 3.41 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 147.65, 134.44, 132.23, 132.17, 128.11, 124.66, 123.60 (q, J=283.8), 70.99 (q, J=32.6 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.47; EIMS m/z 230 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3,5-dimethylphenyl)ethanol

The product was isolated as a white solid (6.49 g, 84%): mp 45-49° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.10 (d, J=6.8 Hz, 2H), 4.89 (m, 1H), 2.63 (d, J=4.3 Hz, 1H), 2.27 (d, J=2.2 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 160.45 (d, J=246.0 Hz), 128.73, 127.97, 124.92 (d, J=18.6 Hz), 124.19 (q, J=279.1 Hz), 72.36 (q, J=32.0 Hz), 14.61 (d, J=4.1 Hz).

¹⁹F NMR (376 MHz, CDCl₃) δ −78.48, −120.14; EIMS m/z 222 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3-methylphenyl)ethanol

The product was isolated as a white solid (2.12 g, 33%): mp 40-46° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.28 (d, J=7.4 Hz, 1H), 7.25-7.14 (m, 1H), 7.01 (t, J=8.9 Hz, 1H), 5.05-4.63 (m, 1H), 3.03 (d, J=4.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 161.91 (d, J=247.0 Hz), 130.62 (d, J=5.6 Hz), 129.41 (d, J=3.5 Hz), 126.55 (d, J=8.5 Hz), 115.19 (d, J=22.9 Hz), 72.23 (q, J=32.1 Hz), 14.44 (d, J=3.6 Hz); ¹⁹F NMR (376 MHz, CDCl₃) 6-78.57, −116.15; EIMS m/z 208 ([M]⁺).

1-(3-Chloro-4-methylphenyl)-2,2,2-trifluoroethanol

The product was isolated as a clear colorless oil (4.99 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.31 (s, 1H), 7.10 (m, 2H), 4.79 (q, J=6.1 Hz, 1H), 2.89 (bs, 1H), 2.25 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 137.64, 134.67, 132.99, 131.09, 128.01, 125.58, 124.02 (q, J=284.8 Hz), 72.08 (q, J=32.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.39; EIMS m/z 224.5 ([M]⁺).

1-(3,4-Dibromophenyl)-2,2,2-trifluoroethanol

The product was isolated as a clear colorless oil (5.92 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=2.0 Hz, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.29 (dd, J=8.3, 2.0 Hz, 1H), 4.99 (qd, J=6.4, 4.2 Hz, 1H), 2.75 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 134.52, 133.81, 132.60, 127.45, 126.19, 125.16, 123.71 (q, J=283.8 Hz)., 71.57 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.44; EIMS m/z 334 ([M]⁺).

2,2,2-Trifluoro-1-(3-(trifluoromethoxy)phenyl)ethanol

The product was isolated as a clear colorless oil (20.9 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 7.55-7.36 (m, 3H), 7.33-7.14 (m, 1H), 5.06 (m, 1H), 2.80 (br m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 149.36 (q, J=2.0 Hz), 136.04, 129.99, 125.78, 123.91 (q, J=282.8 Hz), 121.90, 120.31 (q, J=258.6 Hz), 120.12, 72.04 (q, J=32.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.92, −78.49; EIMS m/z 260 ([M]⁺).

2-Fluoro-5-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile

The product was isolated as a clear colorless oil (5.47 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (dd, J=5.9, 2.2 Hz, 1H), 7.76 (ddd, J=7.8, 5.0, 2.3 Hz, 1H), 7.30 (d, J=8.6 Hz, 1H), δ 5.09 (qd, J=6.3, 4.2 Hz, 1H), 3.12 (bm, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 163.49 (d, J=261.7 Hz), 134.23 (d, J=8.6 Hz), 132.67, 131.17, 123.66 (q, J=282.4 Hz), 116.79 (d, J=20.1 Hz), 113.39, 100.96 (d, J=194.9), 71.07 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.70, −105.22; EIMS m/z 219 ([M]⁺).

1-(3-Bromo-5-chlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a yellow liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.78 (s, 1H), 7.67 (s, 1H), 7.57 (s, 1H), 7.15 (d, J=5.7 Hz, 1H); EIMS m/z 288 ([M]⁺); IR (thin film) 3435, 1175, 750 cm⁻¹.

1-(3-Bromo-5-fluorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.43 (s, 1H), 7.29-7.26 (m, 1H), 7.18 (d, J=8.8 Hz, 1H), 5.03-4.98 (m, 1H), 3.60 (bs, 1H).; EIMS m/z 272.0 ([M]⁺); IR (thin film) 3400, 1176, 520 cm⁻¹.

1-(3,5-Dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-ol

Using pentafluoroethyltrimethylsilane, the product was isolated as a white solid (6.22 g, 88%): mp 71-73° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.42 (t, J=1.9 Hz, 1H), 7.37 (d, J=1.8 Hz, 2H), 5.11 (dt, J=16.2, 5.7 Hz, 1H), 2.62 (d, J=4.9 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 136.90, 135.31, 129.84, 126.38, 70.94 (dd, J=28.2, 23.1 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −81.06, −120.94 (d, J=277.5 Hz), −129.18 (d, J=277.5 Hz); EIMS m/z 295 ([M]⁺).

2,2,3,3,3-Pentafluoro-1-(3,4,5-trichlorophenyl)propan-1-ol

Using pentafluoroethyltrimethylsilane, the product was isolated as an off white semi solid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.78 (s, 2H), 7.29 (d, J=5.4 Hz,), 5.50-5.40 (m, 1H); EIMS m/z 328.0 ([M]⁺); IR (thin film) 3459, 1188, 797 cm⁻¹.

2,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanol

The product was isolated as a light yellow (13.8 g, 89%): ¹H NMR (400 MHz, CDCl₃) δ 7.77 (s, 1H), 7.70-7.67 (m, 2H), 7.55 (t, J=7.8 Hz, 1H), 5.12 (q, J=6.6 Hz, 1H), 2.76 (s, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.8, −78.5; EIMS m/z 244 ([M]⁺).

1-(3,4-Dichloro-5-methylphenyl)-2,2,2-trifluoroethanol

The product was isolated as an off pale yellow solid: ¹H NMR (400 MHz, CDCl₃) δ 7.44 (s, 1H), 7.26 (s, 1H), 4.98-4.95 (m, 1H), 2.61 (d, J=4.4 Hz, 1H), 2.44 (s, 3H).; EIMS m/z 258.1 ([M]⁺); IR (thin film) 3421, 2926, 1129, 748 cm⁻¹.

1-(3-Chloro-5-ethylphenyl)-2,2,2-trifluoroethanol

The product was isolated as an off brown liquid (0.43 g, 85%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.34 (s, 1H), 7.31-7.30 (m, 2H), 6.99 (d, J=5.7 Hz, 1H), 5.23-5.16 (m, 1H), 2.67 (m, 2H), 1.19 (t, J=7.8 Hz, 3H); EIMS m/z 238.0 ([M]⁺); IR (thin film) 3361, 1172, 749 cm⁻¹.

1-(4-Bromo-3,5-dichlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.75 (s, 2H), 7.24 (d, J=6.0 Hz, 1H), 5.34-5.29 (m, 1H); EIMS m/z 321.88 ([M]⁺); IR (thin film) 3420, 1706, 1267, 804, 679 cm⁻¹.

1-(3,5-Dibromo-4-chlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a pale yellow gum: ¹H NMR (300 MHz, DMSO-d₆) δ 7.89 (s, 2H), 7.20 (d, J=6.0 Hz, 1H) 5.34-5.30 (m, 1H); EIMS m/z 366.0 ([M]⁺).

Step 2. 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol (4.0 g, 16.3 mmol) in CH₂Cl₂ (50 mL), were added NBS (2.9 g, 16.3 mmol) and triphenyl phosphite (5.06 g, 16.3 mmol), and the resultant reaction mixture was heated at reflux for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and was concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 100% pentane) afforded the title compound as a liquid (2.0 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 3H), 5.00 (m, 1H); EIMS m/z 306 ([M]⁺).

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 1.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (AI6)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.59 (s, 2H), 5.00 (m, 1H); EIMS m/z 340.00 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (AI7)

The product was isolated as a colorless oil (320 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 2H); EIMS m/z 324.00 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichlorobenzene (AI8)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.63 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H); EIMS m/z 306.00 ([M]⁺).

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 5.04-4.97 (m, 1H); EIMS m/z 394.6 ([M]⁺); IR (thin film) 1114, 535 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluoro-5-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.79-7.77 (m, 2H), 6.40-6.34 (m, 1H); EIMS m/z 324.00 ([M]⁺); IR (thin film) 1175, 525 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.71 (s, 1H), 7.67 (s, 1H), 7.64 (s, 1H), 5.15-5.09 (m, 1H); EIMS m/z 340.00 ([M]⁺); IR (thin film) 1178, 750, 540 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.75-7.72 (m, 2H), 7.28-7.24 (m, 1H), 5.19-5.16 (m, 1H); EIMS m/z 326.0 ([M]⁺); IR (thin film) 1114, 571 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trifluorobenzene

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.23-7.12 (m, 2H), 5.05-4.98 (m, 1H); EIMS m/z 292.0 ([M]⁺); IR (thin film) 1116, 505 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,4-trifluorobenzene

The title molecule was isolated as a colorless oil: ¹H NMR (300 MHz, CDCl₃) δ 7.44 (qd, J=m, 1H), 7.11-7.03 (m, 1H), 5.53-5.45 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4,5-trichlorobenzene

The title molecule was isolated as an off white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.06 (d, J=2.1 Hz, 1H), 7.71 (s, 1H), 6.45-6.37 (m, 1H); EIMS m/z 340.0 ([M]⁺); IR (thin film) 1186, 764, 576 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-nitrobenzene

The title molecule was isolated as an off white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.30 (s, 1H), 7.92 (d, J=9.0 Hz, 1H), 6.43-6.35 (m, 1H); EIMS m/z 317.0 ([M]⁺); IR (thin film) 2927, 1540, 1353, 1177, 766, 530 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluoro-1,3-dimethylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.32 (d, J=7.2 Hz, 2H), 6.15-6.07 (m, 1H), 3.23 (s, 6H); ESIMS m/z 284.1([M+H]⁺); IR (thin film) 2962, 1112, 500 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-methylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.34-7.28 (m, 2H), 7.04-6.98 (m, 1H), 5.10-5.03 (m, 1H), 2.29 (s, 3H); EIMS m/z 270.1([M]⁺); IR (thin film) 2989, 1163 cm⁻¹.

1-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-3,5-dichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.79 (t, J=2.0 Hz, 1H), 7.63 (S, 2H), 6.37-6.29 (m, 1H); EIMS m/z 356([M]⁺); IR (thin film) 1673, 1130, 715, 518 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-methylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.55-7.50 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 6.24-6.16 (m, 1H); IR (thin film) 2983, 1112, 749, 564 cm⁻¹.

1,2-Dibromo-4-(1-bromo-2,2,2-trifluoroethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.75 (s, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.33-7.30 (m, 1H), 5.07-5.00 (m, 1H); EIMS m/z 393.8 ([M]⁺); IR (thin film) 2981, 1644, 1165 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethoxy)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.65-7.60 (m, 2H), 7.56-7.50 (m, 2H), 6.35-6.27 (m, 1H); EIMS m/z 322 ([M]⁺); IR (thin film) 3413, 1161, 564 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzonitrile

The title molecule was isolated as a pale yellow liquid: ¹H NMR (300 MHz, CDCl₃) δ 8.15-8.12 (m, 1H), 8.00-7.98 (m, 1H), 7.69-7.63 (m, 1H), 6.31-6.26 (m, 1H); EIMS m/z 280.9 ([M]⁺).

1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-chlorobenzene

The title molecule was isolated as a pale yellow liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (s, 1H), 7.74 (s, 1H), 7.65 (s, 1H), 6.26-6.20 (m, 1H); EIMS m/z 349.9 ([M]⁺); IR (thin film) 1114, 764 cm⁻¹.

1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-fluorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.43 (s, 1H), 7.32-7.29 (m, 1H), 7.22 (d, J=8.8 Hz, 1H), 1.06 (q, 1H); EIMS m/z 334.0 ([M]⁺); IR (thin film) 3087, 1168, 533 cm⁻¹.

5-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-1,2,3-trichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.85 (s, 2H), 6.38-6.29 (m, 1H); EIMS m/z 389.9 ([M]⁺); IR (thin film) 1208, 798, 560 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-2,6-difluorobenzonitrile

The title molecule was isolated as a purple solid: mp 59-63° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.25 (s, 2H), 5.11-5.07 (m, 1H); ESIMS m/z 299.0 ([M+H]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: mp 59-63° C.; ¹H NMR (300 MHz, CDCl₃) δ 7.75-7.67 (m, 3H), 7.57-7.52 (m, 1H), 5.20-5.13 (m, 1H); ESIMS m/z 306.0 ([M]⁺); IR (thinfilm) 3436, 2925, 1265, 749 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-difluoro-2-methoxybenzene

The title molecule was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.08 (d, J=8.4 Hz, 2H), 5.03-4.98 (m, 1H), 4.04 (s, 3H); ESIMS m/z 304.1 ([M+H]⁺); IR (thinfilm) 1114, 613 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichloro-3-methylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.46 (s, 1H), 7.27 (s, 1H), 5.04-4.99 (m, 1H), 2.44 (s, 3H); EIMS m/z 320.0 ([M]⁺); IR (thinfilm) 2925, 1112, 752, 580 cm⁻¹.

4-(1-Bromo-2,2-difluoropropyl)-1,2-dichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.76-7.70 (m, 2H), 7.54 (dd, J=8.4 1.8 Hz, 1H), 5.81-5.73 (m, 1H), 1.67 (d, J=18.9 Hz, 3H); EIMS m/z 304.0 ([M]⁺); IR (thinfilm) 1118, 800, 499 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-ethylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.43 (d, J=5.6 Hz, 2H), 7.39 (s, 1H), 6.20-6.16 (m, 1H), 2.68-2.62 (m, 2H), 1.19 (t, J=7.6 Hz, 3H); EIMS m/z 300.0 ([M]⁺); IR (thinfilm) 2970, 1167, 716, 539 cm⁻¹.

2-Bromo-5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.79 (s, 2H), 6.27-6.21 (m, 1H); EIMS m/z 383.9 ([M]⁺); IR (thinfilm) 2924, 1114, 749, 534 cm⁻¹.

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2-chlorobenzene

The title molecule was isolated as a pale yellow liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.97 (s, 2H), 6.27-6.19 (m, 1H); EIMS m/z 428.0 ([M]⁺).

Example 2 Preparation of N-Methyl-4-vinylbenzamide (AI9)

Step 1. 4-Vinylbenzoyl chloride (AI10)

To a stirred solution of 4-vinylbenzoic acid (1 g, 6.75 mmol) in CH₂Cl₂ (20 mL) at 0° C. were added a catalytic amount of DMF and oxalyl chloride (1.27 g, 10.12 mmol) dropwise over a period of 15 minutes (min). The reaction mixture was stirred at 25° C. for 6 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure to give the crude acid chloride.

Step 2. N-Methyl-4-vinylbenzamide (AI9)

To 1 M N-methylamine in THF (13.5 mL, 13.5 mmol) at 0° C. were added TEA (1.34 mL, 10.12 mmol) and the acid chloride from Step 1 above in THF (10 mL), and the reaction mixture was stirred at 25° C. for 3 h. After the reaction was deemed complete by TLC, the reaction mixture was quenched with water and then was extracted with EtOAc (3×). The combined EtOAc layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (650 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H); ESIMS m/z 161.95 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in accordance with Example 2.

N,N-Dimethyl-4-vinylbenzamide (AI11)

The product was isolated as an off-white solid (650 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.42 (m, 4H), 6.71 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.31 (d, J=10.8 Hz, 1H), 3.05 (s, 3H), 3.00 (s, 3H); ESIMS m/z 176.01 ([M+H]⁺).

N-(2,2,3-Trifluoromethyl)-4-vinylbenzamide (AI12)

The product was isolated as an off-white solid (900 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.19 (m, 2H); ESIMS m/z 230.06 ([M+H]⁺).

Morpholino(4-vinylphenyl)methanone (AI13)

The product was isolated as a white solid (850 mg, 60%): ESIMS m/z 218.12 ([M+H]⁺).

Example 3 Preparation of Ethyl 2-methyl-4-vinylbenzoate (AI14)

Step 1. 4-Formyl-2-methylbenzoic acid (AI15)

To a stirred solution of 4-bromo-2-methylbenzoic acid (10 g, 46.4 mmol) in dry THF (360 mL) at −78° C. was added n-BuLi (1.6 M solution in hexanes; 58.17 mL, 93.0 mmol) and DMF (8 mL). The reaction mixture was stirred at −78° C. for 1 h then was warmed to 25° C. and stirred for 1 h. The reaction mixture was quenched with 1 N HCl solution and extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure. The residue was washed with n-hexane to afford the title compound as a solid (3.0 g, 40%): mp 196-198° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.32 (br s, 1H), 10.05 (s, 1H), 7.98 (m, 1H), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z 163.00 ([M−H]⁻).

Step 2. Ethyl 4-formyl-2-methylbenzoate (AI16)

To a stirred solution of 4-formyl-2-methylbenzoic acid (3 g, 18.2 mmol) in EtOH (30 mL) was added H₂SO₄ and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with EtOAc and washed with water. The combined EtOAc extracts were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a solid (2.8 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.04 (m, 1H), 7.75 (m, 2H), 4.43 (m, 2H), 2.65 (s, 3H), 1.42 (m, 3H).

Step 3. Ethyl 2-methyl-4-vinylbenzoate (AI14)

To a stirred solution of ethyl 4-formyl-2-methylbenzoate (2.8 g, 4 mmol) in 1,4-dioxane (20 mL) were added K₂CO₃ (3.01 g, 21.87 mmol) and methyltriphenyl phosphonium bromide (7.8 g, 21.87 mmol) at 25° C. Then the reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAc in n-Hexane) to afford the title compound as a solid (2.0 g, 72%): ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd, J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.39 (m, 2H), 2.60 (s, 3H), 1.40 (m, 3H); ESIMS m/z 191.10 ([M−H]⁻); IR (thin film) 2980, 1716, 1257 cm⁻¹.

Example 4 Preparation of tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

Step 1. tert-Butyl 4-bromo-2-chlorobenzoate (AI18)

To a stirred solution of 4-bromo-2-chlorobenzoic acid (5 g, 21.37 mmol) in THF (30 mL) was added di-tert-butyl dicarbonate (25.5 g, 25.58 mmol), TEA (3.2 g, 31.98 mmol) and DMAP (0.78 g, 6.398 mmol), and the reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was diluted with EtOAc and washed with water. The combined organic layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 2-3% EtOAc in n-hexane) to afford the title compound as a liquid (3.2 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ 7.62 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 290.10 ([M+H]⁺); IR(thin film) 1728 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Step 1 of Example 4.

tert-Butyl 2-bromo-4-iodobenzoate (AI19)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 8.01 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 382.10 ([M+H]⁺); IR(thin film) 1727 cm⁻¹.

tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate(AI20)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 7.85 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 1.57 (s, 9H); ESIMS m/z 324.10 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

To a stirred solution of tert-butyl 4-bromo-2-chlorobenzoate (1.6 g, 5.50 mmol) in toluene (20 mL) was added Pd(PPh₃)₄ (0.31 mg, 0.27 mmol), K₂CO₃ (2.27 g, 16.5 mmol) and vinylboronic anhydride pyridine complex (2.0 g, 8.3 mmol) and the reaction mixture was heated to reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 5-6% EtOAc in n-hexane) afforded the title compound as a liquid (0.6 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.1 Hz, 1H), 7.44 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.85 (d, J=17.6 Hz, 1H), 5.40 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 238.95 ([M+H]⁺); IR (thin film) 2931, 1725, 1134 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 4.

tert-Butyl 2-bromo-4-vinylbenzoate (AI21)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 7.68 (m, 2H), 7.36 (d, J=8.0 Hz, 1H), 6.68 (dd, J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 282.10 ([M+H]⁺); IR (thin film) 2978, 1724, 1130 cm⁻¹.

tert-Butyl 2-(trifluoromethyl)-4-vinylbenzoate (AI22)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.71 (d, J=6.4 Hz, 2H), 7.59 (d, J=7.6 Hz, 1H), 6.77 (dd, J=17.6, 10.8 Hz, 1H), 5.89 (d, J=17.6 Hz, 1H), 5.44 (d, J=10.8 Hz, 1H), 1.58 (s, 9H); ESIMS m/z 272.20 ([M+H]⁺); IR (thin film) 2982, 1727, 1159 cm⁻¹.

Example 5 Preparation of tert-Butyl 2-cyano-4-vinylbenzoate (AI23)

To a stirred solution of tert-butyl 2-bromo-4-vinylbenzoate (0.5 g, 1.77 mmol) in DMF (20 mL) was added CuCN (0.23 g, 2.65 mmol), and the reaction mixture was heated at 140° C. for 3 h. The reaction mixture was cooled to 25° C., diluted with water, and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 15% EtOAc in n-hexane) to afford the title compound as a white solid (0.3 g, 72%): mp 51-53° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.03 (s, 1H), 7.77 (s, 1H), 7.64 (d, J=8.4 Hz, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.93 (d, J=17.6 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 229.84 ([M+H]⁺); IR (thin film) 2370, 1709, 1142 cm⁻¹.

Example 6 Preparation of Ethyl 2-bromo-4-iodobenzoate (AI46)

To a stirred solution of 4-iodo-2-bromobenzoic acid (5 g, 15.29 mmol) in EtOH (100 mL) was added H₂SO₄ (5 mL), and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with EtOAc (2×100 mL) and washed with water (100 mL). The combined EtOAc extracts were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the compound as a pale yellow solid (5 g, 92%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.04 (d, J=1.2 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H).

The following compounds were made in accordance with the procedures disclosed in Example 6.

Ethyl 4-bromo-2-chlorobenzoate (AI47)

The title compound was isolated as an off-white solid (2.0 g, 80%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.25 (d, J=1.2 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 4.65 (q, J=7.2 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H).

Ethyl 4-bromo-2-methylbenzoate (AI48)

The title compound was isolated as a pale yellow liquid (3.0 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.4 Hz, 1H), 7.41 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.40 (t, J=7.2 Hz, 3H)ESIMS m/z 229.11 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Ethyl 4-bromo-2-fluorolbenzoate (AI49)

The title compound was isolated as a colorless liquid (9.0 g, 79%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.84 (t, J=8.4 Hz, 1H), 7.76 (d, J=2.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H); ESIMS m/z 246.99 ([M+H]⁺), IR (thin film) 1734 cm⁻¹.

Example 7 Preparation of Ethyl 4-bromo-2-ethylbenzoate (AI50)

To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.17 mmol) in THF (16 mL), was added 1.0 M ethyl magnesium bromide in THF (32 mL, 32.0 mmol) dropwise at 0° C. and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was quenched with 2 N HCl and extracted with EtOAc. The combined EtOAc layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude 4-bromo-2-ethylbenzoic acid as a colorless liquid that was used in the next step without purification (0.4 g): ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J=8.4 Hz, 1H), 7.47 (m, 1H), 7.43 (m, 1H), 2.95 (q, J=4.0 Hz, 2H), 1.32 (t, J=4.0 Hz, 3H); ESIMS m/z 228.97 ([M+H]⁺).

The title compound was synthesized from 4-bromo-2-ethylbenzoic acid in accordance to the procedure in Example 6, isolated as a colorless liquid (0.15 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.47 (m, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.06 (q, J=7.6 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 226.96 ([M−H]⁻);

IR (thin film) 3443, 1686, 568 cm⁻¹.

Example 8 Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51)

To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs₂CO₃ (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl₂ (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to ambient temperature and filtered through a Celite® bed and washed with EtOAc. The filtrate was again extracted with EtOAc and the combined organic layers washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]⁺); IR (thin film) 1729 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 8.

Ethyl 2-methyl-4-vinylbenzoate (AI52)

The title compound was isolated as a colorless liquid (0.8 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.27 (m, 2H), 6.79 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 191.10 ([M+H]⁺); IR (thin film) 1717, 1257 cm⁻¹.

Ethyl 2-fluoro-4-vinylbenzoate (AI53)

The title compound was isolated as a pale yellow liquid (2.0 g, 50%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.87 (t, J=8.0 Hz, 1H), 7.51 (d, J=16.0 Hz, 1H), 7.48 (d, J=16.0 Hz, 1H), 6.82 (dd, J=17.6, 10.8 Hz, 1H), 6.09 (d, J=17.6 Hz, 1H), 5.50 (d, J=10.8 Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H); ESIMS m/z 195.19 ([M+H]⁺); IR (thin film) 1728 cm⁻¹.

Example 9 Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54)

To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and K₂CO₃ (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (2×50 mL), washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]⁺); IR (thin film) 1729, 886 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 9.

Ethyl 2-ethyl-4-vinylbenzoate (AI55)

The title compound was isolated as a color less liquid (1.0 g, 66%): ¹H NMR (300 MHz, CDCl₃) δ 7.85 (m, 1H), 7.29 (m, 2H), 6.76 (d, J=10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.36 (d, J=10.5 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 3.10 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H); ESIMS m/z 205.26 ([M+H]⁺); IR (thin film) 1720, 1607, 1263 cm⁻¹.

Methyl 2-methoxy-4-vinylbenzoate (AI56)

The title compound was isolated as a pale yellow liquid (1.2 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.04 (d, J=1.2 Hz, 1H), 6.97 (s, 1H), 6.74 (dd, J=11.2, 11.2 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.39 (d, J=17.6 Hz, 1H) 3.93 (s, 3H), 3.91 (s, 3H); ESIMS m/z 193.18 ([M+H]⁺); IR (thin film) 1732 cm⁻¹

Ethyl 2-(methylthio)-4-vinylbenzoate

The title compound was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.98 (d, J=8.4 Hz, 1H), 7.23-7.18 (m, 2H), 6.78 (dd, J=17.7, 10.8, Hz, 1H), 5.89 (d, J=17.4 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.39-4.36 (m, 2H), 2.48 (s, 3H), 1.39 (t, J=6.9 Hz, 3H); ESIMS m/z 221.9 ([M+H]⁺); IR (thin film) 1708 cm⁻¹

Example 10 Preparation of (E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (AI24)

To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (2.0 g, 10.5 mmol) in 1,2-dichlorobenzene (25 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (6.44 g, 21.0 mmol), CuCl (208 mg, 21 mmol) and 2,2bipyridyl (0.65 g, 4.1 mmol). The reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAc in petroleum ether) afforded the title compound as a solid (1.7 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.91 (d, J=8.0 Hz, 1H), 7.37 (m, 1H), 7.27-7.24 (m, 4H), 6.59 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.08 (m, 1H), 2.62 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 415.06 ([M−H]⁻); IR (thin film) 1717, 1255, 1114 cm⁻¹.

Compounds AI25, AI57-AI68 and AC1-AC5 (Table 1) were made in accordance with the procedures disclosed in Example 10.

(E)-Ethyl 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)-benzoic acid (AI25)

The product was isolated as a pale brown gummy liquid (500 mg, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (m, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.42 (s, 2H), 6.70 (d, J=16.0 Hz, 1H), 6.57 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 1.40 (t, J=7.6 Hz, 3H),; ESIMS m/z 502.99 ([M−H]⁻); IR (thin film) 1730, 1201, 1120, 749 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoate (AI57)

¹H NMR (400 MHz, CDCl₃) δ 7.38 (s, 1H), 7.26 (s, 3H), 7.21 (d, J=8.4 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.47 (dd, J=, 16.0, 8.0 Hz, 1H), 4.41 (q, J=6.8 Hz, 2H), 4.18 (m, 1H), 1.41 (t, J=6.8 Hz, 3H); ESIMS m/z 419.33 ([M−H]⁻); IR (thin film) 1723, 1115, 802 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-bromobenzoate (AI58)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.38 (m, 2H), 7.26 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.39 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 481.22 ([M−H]⁻); IR (thin film) 1727, 1114, 801, 685 cm⁻¹.

(E)-Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI59)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.36 (d, J=1.6 Hz, 1H), 6.56 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 514.74 ([M−H]⁻);

IR (thin film) 1726, 1115, 808, 620 cm⁻¹.

(E)-Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI60)

The title compound was isolated as a light brown gummy material: ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H).

(E)-Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (AI61)

¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J=8.0 Hz, 1H), 7.46 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.31 (d, J=1.6 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 470.73 ([M−H]⁻); IR (thin film) 1726, 1115, 809, 3072 cm⁻¹.

(E)-Ethyl 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoate (AI62)

The title compound was isolated as a pale brown liquid (1.0 g, 46.3%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (s, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.41 (s, 2H) 6.65 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=7.6 Hz, 3H); ESIMS m/z 502.99 ([M−H]⁻); IR (thin film) 1730, 1202, 1120, 750 cm⁻¹.

(E)-Ethyl 2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI63)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 2H), 7.34 (m, 1H), 7.24 (m, 1H), 6.57 (d, J=16.2 Hz, 1H), 6.45 (dd, J=16.2, 7.2 Hz, 1H), 4.43 (q, J=7.2 Hz, 2H), 4.13 (m, 1H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-Ethyl 2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI64)

¹H NMR (400 MHz, CDCl₃) δ 7.93 (t, J=7.6 Hz, 1H), 7.34 (d, J=5.6 Hz, 2H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.13 (m, 1H), 1.41 (t, J=7.6 Hz, 3H); ESIMS m/z 436.81 ([M−H]⁻); IR (thin film) 1725 cm⁻¹.

(E)-Ethyl 2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI65)

¹H NMR (400 MHz, CDCl₃) δ 7.94 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.36 (m, 3H), 6.56 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 498.74 ([M−H]⁻); IR (thin film) 1726, 1114, 820, 623 cm⁻¹.

(E)-Ethyl 2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI66)

The title compound was isolated as a brown semi-solid: ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 432.90 ([M−H]⁻); IR (thin film) 1715 cm⁻¹.

(E)-Methyl 2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI67)

¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.4 Hz, 1H), 7.35 (d, J=6.0 Hz, 2H), 7.03 (d, J=1.2 Hz, 1H), 6.92 (s, 1H), 6.59 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H); ESIMS m/z 437.29 ([M+H]⁺); IR (thin film) 1724 cm⁻¹.

(E)-Ethyl 2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI68)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz, 2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.14 (m, 1H), 3.01 (q, J=7.6 Hz 2H), 1.41 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 447.05 ([M−H]⁻); IR (thin film) 1715, 1115, 817 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(methylthio)benzoate

Isolated as a brown liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.1 Hz, 2H), 7.35-7.32 (m, 2H), 7.21-7.16 (m, 2H), 6.63 (d, J=15.8 Hz, 1H), 6.45 (dd, J=15.9, 7.8 Hz, 1H), 4.41-4.31 (m, 2H), 4.30-4.10 (m, 1H), 2.47 (s, 3H), 1.40 (t, J=7.5 Hz, 3H); ESIMS m/z 466.88 ([M+H]⁺); IR (thin film) 1705, 1114 cm⁻¹.

(E)-Ethyl 2-bromo-4-(3-(3,5-difluoro-4-methoxyphenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoate

The product was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J=8.0 Hz, 1H), 7.66 (d, J=1.6 Hz, 1H), 7.35-7.33 (m, 1H), 6.96-6.90 (m, 2H), 6.54 (d, J=15.6 Hz, 1H), 6.43 (dd, J=15.6, 8.0 Hz, 1H), 4.39 (q, J=6.8 Hz, 2H), 4.09-4.05 (m, 1H), 4.02 (s, 3H), 1.40 (t, J=7.2 Hz, 3H); EIMS m/z 478.2 ([M]⁺); IR (thin film) 1727, 1113 cm⁻¹.

Example 11 Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI32)

To a stirred solution of (E)-ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added 11 N HCl (30 mL), and the reaction mixture was heated at 100° C. for 48 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with water and extracted with chloroform (CHCl₃). The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure, and the crude compound was washed with n-hexane to afford the title compound as a white solid (0.7 g, 50%): mp 142-143° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 12.62 (br s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.66 (s, 3H), 7.52-7.44 (m, 2H), 6.89 (dd, J=16.0, 8.0 Hz, 1H), 6.78-6.74 (d, J=16.0 Hz, 1H), 4.84 (m, 1H), 2.50 (s, 3H); ESIMS m/z 387.05 ([M−H]⁻); IR (thin film) 3448, 1701, 1109, 777 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 11.

(E)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI26)

The product was isolated as a pale brown gummy liquid (1 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.50 (s, 3H); ESIMS m/z 422.67 ([M−H]⁻).

(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI27)

The product was isolated as an off-white semi-solid (1 g, 45%): ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.4 Hz, 1H), 7.50 (m, 1H), 7.40 (s, 1H), 7.36 (m, 2H), 6.59 (d, J=15.6 Hz, 1H), 6.48 (dd, J=15.6, 7.6 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 442.72 ([M−H]⁻); IR (thin film) 3472, 1704, 1113, 808 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI28)

The product was isolated as a brown solid (1 g, 45%): mp 70-71° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m, 3H), 6.58 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 484.75 ([M−H]⁻); IR (thin film) 3468, 1700 cm⁻¹.

(E)-2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI29)

The product was isolated as an off-white solid (500 mg, 45%): mp 100-101° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 431.93 ([M−H]⁻).

E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI30)

The product was isolated as a pale brown liquid (500 mg, 46%): ¹H NMR (400 MHz, CDCl₃) δ 8.03 (m, 1H), 7.49 (m, 2H), 7.29 (m, 1H), 7.22 (m, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.64 (s, 3H); ESIMS m/z 386.84 ([M−H]⁻); IR (thin film) 3428, 1690, 1113, 780 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI31)

The product was isolated as a white solid (500 mg, 50%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.61 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M−H]⁻).

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoic acid (AI33)

The product was isolated as a white solid (500 mg, 45%): mp 142-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 474.87 ([M−H]⁻).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI69)

The title compound was isolated as a brown solid (0.8 g, 28%): ¹H NMR (400 MHz, CDCl₃) δ 13.42 (br, 1H), 7.98 (d, J=1.5 Hz, 1H), 7.94 (m, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.65 (m, 1H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.80 (d, J=15.9 Hz, 1H), 4.91 (m, 1H); ESIMS m/z 484.75 ([M−H]⁻); IR (thin film) 3469, 1700 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluo robut-1-enyl)benzoic acid (AI70)

The title compound was isolated as a yellow liquid (0.3 g, crude): ¹H NMR (300 MHz, CDCl₃) δ 7.79 (d, J=8.1 Hz, 1H), 7.67 (s, 1H), 7.34 (m, 3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.6 Hz, 1H), 4.43 (m, 1H); ESIMS m/z 471.0 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-ethylbenzoic acid (AI71)

The title compound was isolated as a brown gummy material (0.2 g, crude): ¹H NMR (300 MHz, DMSO-d₆) δ 12.5 (br, 1H), 7.85 (d, J=6.3 Hz, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.52 (m, 2H), 6.96 (dd, J=8.7, 8.7 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.80 (m, 1H), 4.06 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H); ESIMS m/z 419.06 ([M−H]⁻).

(E)-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (AI72)

The title compound was isolated as a yellow liquid (0.7 g, 95%): ¹H NMR (300 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 1H), 7.41 (s, 3H), 6.57 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI73)

The title compound was isolated as a light brown gummy material (0.7 g, 38%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.10 (d, J=16.0 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M−H]⁻).

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoic acid (AI74)

The title compound was isolated as a light brown liquid (0.3 g, crude): ESIMS m/z 393.15 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (AI75)

The title compound was isolated as a light brown liquid (0.35 g, crude): ESIMS m/z 451.91 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(methylthio)benzoic acid

¹H NMR (400 MHz, CDCl₃) δ 7.88-7.85 (m, 3H), 7.46 (d, J=6.8 Hz, 1H), 7.37 (s, 1H), 6.99 (dd, J=15.6, 8.8 Hz, 1H), 6.85 (d, J=16.0 Hz, 1H), 4.85-4.81 (m, 2H), 2.45 (s, 3H); ESIMS m/z 436.89 ([M−H]⁻); IR (thinfilm) 3469, 1686, 1259, 714 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-difluoro-4-methoxyphenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.48 (bs, 1H), 8.03 (s, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.69 (d, J=8.1 Hz, 1H), 7.48 (d, J=9.3 Hz, 2H), 7.05 (dd, J=15.6, 9.0 Hz, 1H), 6.83 (d, J=15.9 Hz, 1H), 4.86-4.74 (m, 1H), 4.00 (s, 3H); EIMS m/z 451.18 ([M]⁺); IR (thin film) 3431, 1132 cm⁻¹.

Prophetically, compounds AI34, AI36-AI41, AI44-AI45 (Table 1) could be made in accordance with the procedures disclosed in Example 10, or Examples 10 and 11.

Example 12 Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,2-trifluoroethyl)benzamide (AC6)

To a stirred solution of (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid in DMF was added 2,2,2-trifluoroethylamine, HOBt.H₂O, EDC.HCl and DIPEA, and the reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with hexane:EtOAc afforded a white semi-solid (110 mg, 50%): ¹H NMR (400 MHz, CDCl₃) 7.40 (m, 2H), 7.26 (m, 3H), 6.56 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMS m/z 468.40 ([M−H]⁻); IR (thin film) 1657, 1113, 804 cm⁻¹.

Compounds AC7-AC38, AC40-AC58, AC110-AC112, AC117, and AC118 (Table 1) were made in accordance with the procedures disclosed in Example 12.

Example 13 Preparation of 4-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-((pyrimidin-5-yl)methyl)benzamide (AC39)

To a stirred solution of (pyrimidin-5-yl)methanamine (0.15 g, 1.43 mmol) in CH₂Cl₂ (10 mL) was added drop wise trimethylaluminum (2 M solution in toluene; 0.71 mL, 1.43 mmol), and the reaction mixture was stirred at 25° C. for 30 min A solution of ethyl 4-((E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (0.3 g, 0.71 mmol) in CH₂Cl₂ was added drop wise to the reaction mixture at 25° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 0.5 N HCl solution (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the title compound (0.18 g, 55%): mp 141-144° C.; ¹H (400 MHz, CDCl₃) δ 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.40 (dd, J=16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H); ESIMS m/z 477.83 ([M−H]⁻).

Example 14 Preparation of (E)-2-Chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC64)

To a stirred solution of glycine amide (0.15 g, 0.58 mmol) in CH₂Cl₂ (5 mL) was added trimethylaluminum (2 M solution in toluene; 1.45 mL, 2.91 mmol) dropwise, and the reaction mixture was stirred at 28° C. for 30 min A solution of (E)-ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (0.3 g, 0.58 mmol) in CH₂Cl₂ (5 mL) was added drop wise to the reaction mixture at 28° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 1N HCl solution (50 mL) and extracted with CH₂Cl₂ (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the title compound as yellow solid (0.15 g, 50%): mp 83-85° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J=6.8 Hz, 1H), 7.05 (t, J=5.2 Hz, 1H), 6.70 (t, J=5.2 Hz, 1H), 6.57 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.23 (d, J=5.6 Hz, 2H), 4.15 (m, 1H), 4.01 (m, 2H); ESIMS m/z 580.72 ([M−H]⁻).

Compounds AC59-AC75 (Table 1) were made in accordance with the procedures disclosed in Example 14.

Example 15 Preparation of (E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (AC79)

To a stirred solution of (E)-2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (300 mg, 0.638 mmol) in CH₂Cl₂ (5.0 mL) was added 2-amino-N-(2,2,2-trifluoroethyl)acetamide (172. mg, 0.638 mmol) followed by PyBOP (364.5 mg, 0.701 mmol) and DIPEA (0.32 mL, 1.914 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 40% EtOAc/petroleum ether) afforded the title compound as an off-white solid (121 mg, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.69 (t, J=6.0 Hz, 1H), 8.58 (t, J=6.0 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J=6.4 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.83 (t, J=8.0 Hz, 1H), 3.98 (m, 4H); ESIMS m/z 610.97 ([M+H]⁺); IR (thin film) 3303, 1658, 1166, 817 cm⁻¹.

Compounds AC76-AC80, AC96-AC102, and AC113 (Table 1) were made in accordance with the procedures disclosed in Example 15.

Example 16 Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(1,1-dioxidothietan-3-yl)-2-fluorobenzamide (AC83)

To a stirred solution of (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluoro-N-(thietan-3-yl)benzamide (100 mg, 0.2159 mmol) in acetone/water (1:1, 5.0 mL) was added oxone (266 mg, 0.4319 mmol) and the resultant reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% EtOAc/pet ether) afforded the title compound as an off white solid (70.0 mg, 66%): ¹H NMR (400 MHz, CDCl₃) δ 8.07 (t, J=8.4 Hz, 1H), 7.39 (t, J=1.6 Hz, 1H), 7.31 (d, J=1.2 Hz, 1H), 7.26 (m, 2H), 7.23 (m, 2H), 7.19 (d, J=1.6 Hz, 1H), 6.60 (d, J=16.8 Hz, 1H), 6.49 (dd, J=16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H),; ESIMS m/z 493.83 ([M−H]⁻); IR (thin film) 1527, 1113, 801, 1167, 1321 cm⁻¹.

Compounds AC81-AC87 (Table 1) were made in accordance with the procedures disclosed in Example 16.

Example 17 Preparation of (E)-N-((5-Cyclopropyl-1,3,4-oxadiazol-2-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzamide (AC89)

A solution of (E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (200 mg, 0.379 mmol) in phosphoryl chloride (POCl₃, 2.0 mL) was stirred at ambient temperature for 10 min, then the resultant reaction mixture was heated to 50° C. for 1 h. The reaction mixture was quenched with ice water at 0° C. and extracted with EtOAc. The combined EtOAc layer was washed with saturated sodium bicarbonate (NaHCO₃) solution and brine solution, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 50% EtOAc/pet ether) afforded the title compound as a light brown gummy material (70.0 mg, 36%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (m, 2H), 7.27 (m, 2H), 7.23 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.41 (dd, J=16.0, 7.6 Hz, 1H), 4.79 (d, J=5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H); ESIMS m/z 509.89 ([M+H]⁺); IR (thin film) 1666, 1166, 1112, 800 cm⁻¹.

Example 18 Preparation of (E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzothioamide (AC90)

To a stirred solution of (E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg, 0.638 mmol) in 5 mL of THF at ambient temperature was added 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's reagent) (336 mg, 0.830 mmol) in one portion. The resulting reaction mixture was stirred for 18 h. TLC showed the reaction was not complete, therefore additional Lawesson's reagent (168 mg, 0.415 mmol) was added and reaction stirred for 48 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compound as a yellow glassy oil (188 mg, 44.7%): ¹H NMR (400 MHz, CDCl₃) δ 8.34 (m, 1H), 8.27 (m, 1H), 7.60 (d, J=1.6 Hz, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.40 (s, 2H), 7.36 (dd, J=8.2, 1.7 Hz, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.89 (d, J=8.4, 5.5 Hz, 2H), 4.48 (qd, J=9.0, 6.0 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 656.9 ([M−H]⁻).

Example 19 Preparation of (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenylthioamido)-N-(2,2,2-trifluoroethyl)acetamide (AC91)

To a stirred solution of (E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg, 0.638 mmol) in 5 mL of THF at ambient temperature was added Lawesson's reagent (64.5 mg, 0.160 mmol) in one portion. The resulting reaction mixture was stirred for 18 h, after which time, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compounds as a yellow oil (18.5 mg, 4.51%): ¹H NMR (400 MHz, CDCl₃) δ 8.18 (t, J=5.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J=8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, J=15.9, 7.9 Hz, 1H), 4.54 (d, J=4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, J=8.9, 6.5 Hz, 2H); ESIMS m/z 640.9 ([M−H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 19.

(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC92)

The product was isolated as a colorless oil (17.9 mg, 4.36%): ¹H NMR (400 MHz, CDCl₃) δ 9.16 (d, J=6.1 Hz, 1H), 7.65 (d, J=1.6 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J=5.6 Hz, 1H), 6.55 (d, J=15.9 Hz, 1H), 6.41 (dd, J=15.9, 7.8 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.45 (qd, J=9.0, 6.0 Hz, 2H), 4.12 (q, J=7.2 Hz, 1H); ESIMS m/z 640.9 ([M−H]⁻).

Example 106 Preparation of Ethyl (Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate (AI76)

The title compound was made in accordance with the procedure disclosed in Example 88 and was isolated as a yellow viscous oil (416 mg, 23%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.0 Hz, 1H), 7.40 (d, J=1.7 Hz, 1H), 7.35 (s, 2H), 7.12 (dd, J=8.0, 1.7 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.23-5.91 (m, 1H), 4.42 (q, J=7.1 Hz, 2H), 4.33-4.10 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.34 (d, J=8.3 Hz); EIMS m/z 514.10 ([M]⁻); IR (thin film) 2983, 1727, 1247, 1204, 1116 cm⁻¹.

Example 107 Preparation of (Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (AI77)

To a stirred solution of (Z)-ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate (360 mg, 0.70 mmol) in CH₃CN (1.0 mL) was added iodotrimethylsilane (0.28 mL, 2.8 mmol). The reaction mixture was heated to reflux for 20 h, allowed to cool to ambient temperature and partitioned between CH₂Cl₂ and aqueous 10% sodium thiosulfate (Na₂S₂O₃). The organic phase was washed once with aqueous 10% Na₂S₂O₃ and dried over magnesium sulfate (MgSO₄) and concentrated in vacuo. Passing the material through a silica plug with 10% EtOAc in hexanes, followed by 20% MeOH in CH₂Cl₂) as the eluting solvents afforded the title compound as a yellow foam (143 mg, 42%): mp 54-64° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.36 (s, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 2H), 7.14 (d, J=7.9 Hz, 1H), 6.85 (d, J=11.4 Hz, 1H), 6.15 (t, J=10.9 Hz, 1H), 4.36-4.09 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.30.

Example 108 Preparation of (Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC95)

To a stirred solution of (Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added carbonyldiimidazole (82 mg, 0.51 mmol). The mixture was heated in a 50° C. oil bath for 1.5 h, treated with 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (109 mg, 0.057 mmol) and the resulting mixture heated to reflux for 8 h. After cooling to ambient temperature, the mixture was taken up in Et₂O and washed twice with aqueous 5% sodium bisulfate (NaHSO₄) (2×) and once with saturated NaCl (1×). After dying over MgSO₄, concentration in vacuo and purification by medium pressure chromatography on silica with EtOAc/Hexanes as the eluents, the title compound was obtained as a white foam (160 mg, 41%) mp 48-61° C.: ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J=7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14 (dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.76 (t, J=5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J=5.5 Hz, 1H), 3.98 (qd, J=9.0, 6.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.31, −72.3; EIMS m/z 626.9 ([M+H]⁺).

Example 109a Preparation of (E)-2-Bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC114)

(E)-tert-Butyl 4-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)piperidine-1-carboxylate (0.75 g, 1.11 mmol) was added to dioxane HCl (10 mL) at 0° C. and was stirred for 18 h. The reaction mixture was concentrated under reduced pressure and triturated with diethylether to afford the compound as a light brown solid (0.6 g, 88%).

Example 109b Preparation of (E)-N-(1-Acetylpiperidin-4-yl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC103)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in CH₂Cl₂ (10.0 mL) was added TEA (0.046 mL, 0.35 mmol) and stirred for 10 min. Then acetyl chloride (0.014, 0.18 mmol) was added and stirred for 16 h at ambient temperature. The reaction mixture was diluted with CH₂Cl₂ and washed with saturated NaHCO₃ solution and brine solution. The combined CH₂Cl₂ layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was washed with 5% Et₂O/n-pentane to afford the title compound as a white solid (0.054 g, 50%).

Example 110 Preparation of (E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(3,3,3-trifluoropropanoyl)piperidin-4-yl)benzamide (AC104)

To a stirred solution of 3,3,3-trifluoropropanoic acid (0.02 g, 0.16 mmol) in CH₂Cl₂ (10.0 mL), (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol), PYBOP (0.09 g, 0.17 mmol), and DIPEA (0.06 g, 0.48 mmol) were added at ambient temperature. The reaction mixture was stirred at ambient temperature for 5 h. The reaction mixture was diluted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with 3N HCl and saturated NaHCO₃ solution, the separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% MeOH in CH₂Cl₂) to afford the title compound as an off white gummy material (0.035 g, 29. %).

Example 111 Preparation of (E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)benzamide (AC105)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in THF (5.0 mL) was added TEA (0.06 mL, 0.64 mmol) and stirred for 10 min. Then 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.03, 0.16 mmol) was added and stirred for 16 h at ambient temperature. The reaction mixture was diluted with EtOAc and washed with saturated NaHCO₃ solution and brine solution. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a brown solid (0.05 g, 44%).

Example 112 Preparation of (E)-2-Bromo-N-(1-methylpiperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC106)

A solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol), formaldehyde (30% in water) (0.1 mL, 0.16 mmol) and AcOH (0.01 mL) in MeOH (5.0 mL) was stirred at ambient temperature for 30 min. After that NaBH₃CN (0.01 g, 0.16 mmol) was added at 0° C. and the reaction was stirred for 8 h at ambient temperature. The solvent was removed under reduced pressure to obtain residue which was diluted with EtOAc and washed with saturated aqueous NaHCO₃ solution and brine solution. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to obtain a residue, which was triturated with Et₂O/pentane to afford the title compound as a pale yellow gummy material (0.06 g, 59%).

Example 113 Preparation of ((E)-2-Bromo-N-(1-(cyanomethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC107)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-bromoacetonitrile (0.07, 0.65 mmol) was added and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted with EtOAc and washed with saturated brine solution. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.125 g, 46.8%).

Example 114 Preparation of (E)-2-Bromo-N-(1-(oxetan-3-yl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC108)

A solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.2 g, 0.35 mmol), oxetan-3-one (0.027 g, 0.38 mmol) and AcOH (0.01 mL) in MeOH (5.0 mL) was stirred at ambient temperature for 30 min. After that NaBH₃CN (0.022 g, 0.35 mmol) was added at 0° C. slowly lot wise over the period of 10 min and the reaction was stirred for 8 h at ambient temperature. The solvent was removed under reduced pressure to obtain a residue which was diluted with EtOAc and washed with saturated NaHCO₃ solution and brine solution. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to obtain a residue, which was triturated with Et₂O/pentane to afford the title compound as an off-white solid (0.05 g, 23%).

Example 115 Preparation of (E)-2-Bromo-N-(1-(2-hydroxyethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC109)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-chloroethanol (0.05, 0.65 mmol) was added and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted with EtOAc and washed with saturated brine solution. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.09 g, 34%).

Example 116 Preparation of (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)acetic acid (AI78)

To a stirred solution of (E)-tert-butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetate (440 mg, 0.734 mmol) in CH₂Cl₂ (36.0 ml), was added TFA (4.0 mL) and the reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was concentrated under reduced pressure to obtain residue which was washed with n-pentane to afford the title compound as an off-white solid (310 mg, 78%): ¹H NMR (400 MHz, CDCl₃) δ 13.0 (s, 1H), 8.75 (t, J=5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, J=7.5 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H), 6.96 (dd, J=15.3, 9.3 Hz, 1H), 6.78 (d, J=15.3 Hz, 1H), 4.83 (m, 1H), 3.90 (d, J=5.7 Hz, 2H); ESIMS m/z 543.61 ([M+H]⁺); IR (thin film) 3429, 1635, 1114, 772 cm⁻¹.

Example 117 Preparation of (E)-N-((6-Chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzothioamide (AC115)

To the stirred solution of (E)-N-((6-chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (0.06 g, 0.117 mmol) in toluene (3 mL) was added Lawesson's reagent (0.14 g, 0.351 mmol) and the reaction was irradiated at 100° C. for 1 h, then cooled to ambient temperature and concentrated under reduced pressure to provide crude compound. The crude product was purified by preparative HPLC to afford the product as yellow color solid (0.03 g, 49%).

Example 118 Preparation of (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide (AC116)

Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79)

To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and K₂CO₃ (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with EtOAc (2×50 mL), washed with brine, and dried over Na₂SO₄. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]⁺).

Step 2. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acid (AI80)

To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic acid (0.356 g, 1.53 mmol) in 1N methylpyrrolidine (5.0 mL) was added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g, 3.07 mmol), CuCl (0.03 g, 0.307 mmol) and 2,2 bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at 150° C. for 1 h. After the reaction was complete by TLC, the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.3 g, 21%): ¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35 (s, 3H), 6.63 (d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 474.81 ([M−H]⁻).

Step 3. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)-2-(trifluoromethoxy)benzamide (AC116)

A mixture of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acid (0.25 g, 0.52 mmol), 2-amino-N-(2,2,2-trifluoroethyl)acetamide (0.158 g, 0.62 mmol), PyBOP (0.40 g, 0.78 mmol) and DIPEA (0.134 g, 1.04 mmol) in CH₂Cl₂ (10.0 mL) were stirred at ambient temperature for 16 h. The reaction mixture was diluted with water and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 20% EtOAc/pet ether) afforded the title compound as a pale yellow gummy material (0.15 g, 47%).

The following molecules were made in accordance with the procedures disclosed in Example 118, Step 2:

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (400 MHz, DMSO-d₆) δ 12.90 (bs, 1H), 7.85 (s, 1H), 7.78-7.75 (m, 3H), 7.47-7.41 (m, 2H), 6.89 (dd, J=15.6, 9.2 Hz, 1H), 6.72 (d, J=15.6 Hz, 1H), 4.80-4.75 (m, 1H), 2.33 (s, 3H); ESIMS m/z 474.90 ([M−H]⁻); IR (thin film) 3437, 1689, 1165, 579 cm⁻¹.

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.5 (bs, 1H), 8.03 (s, 1H), 7.95-7.85 (m, 4H), 7.81 (d, J=7.8 Hz, 1H), 7.14 (dd, J=15.6, 9.6 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H), 4.86-4.79 (m, 1H); ESIMS m/z 528.82 ([M−H]⁺); IR (thin film) 3437, 1707, 1153, 555 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.90 (bs, 1H), 7.98 (s, 1H), 7.88 (s, 1H), 7.84 (s, 2H), 7.74 (d, J=7.6 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.04 (dd, J=15.6, 8.8 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.80-4.78 (m, 1H); ESIMS m/z 538.74 ([M−H]⁻); IR (thin film) 3424, 1695, 1168, 578 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-fluoro-5-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.3 (bs, 1H), 7.93 (s, 1H), 7.82-7.77 (m, 2H), 7.72-7.66 (m, 2H), 7.59 (d, J=8.0 Hz, 1H), 7.03 (dd, J=15.6, 9.2 Hz, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.94-4.90 (m, 1H); ESIMS m/z 469.02 ([M−H]⁻); IR (thin film) 3444, 1704, 1172, 513 cm⁻¹.

(E)-4-(3-(3,5-Bis(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-bromobenzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (400 MHz, CDCl₃) δ 7.98 (d, J=7.6 Hz, 1H), 7.92 (s, 1H), 7.83 (s, 2H), 7.73 (d, J=1.6 Hz, 1H), 7.42-7.40 (m, 1H), 6.62 (d, J=16.4 Hz, 1H), 6.55 (dd, J=16.0, 8.0 Hz, 1H), 4.40-4.30 (m, 1H); ESIMS m/z 518.94 ([M−H]⁻); IR (thin film) 3447, 1705, 1171, 526 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.97-7.87 (m, 3H), 7.78-7.61 (m, 4H), 7.08 (dd, J=15.9, 9.3 Hz, 1H), 6.81 (d, J=15.9 Hz, 1H), 4.97-4.84 (m, 1H); ESIMS m/z 518.94 ([M−H]⁻); IR (thin film) 3447, 1705, 1171, 526 cm⁻¹.

(E)-2-Bromo-4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a pale yellow gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.9 (s, 1H), 8.03 (s, 1H), 7.96-7.91 (m, 3H), 7.72 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H), 7.11 (dd, J=15.9, 9.6 Hz, 1H), 6.79 (d, J=15.9 Hz, 1H), 4.98-4.91 (m, 1H); ESIMS m/z 484.94 ([M−H]⁻); IR (thin film) 3444, 1705, 1171, 764 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 8.00 (d, J=8.1 Hz, 1H), 7.71 (s, 1H), 7.61-7.59 (m, 2H), 7.41 (d, J=8.1 Hz, 1H), 7.30-7.24 (m, 1H), 6.59 (dd, J=16.2, 6.0 Hz, 1H), 6.48 (d, J=16.5 Hz, 1H), 4.26-4.21 (m, 1H); ESIMS m/z 469.0 ([M−H]⁻); IR (thin film) 3444, 1699, 1327 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.60 (bs, 1H), 7.97 (s, 2H), 7.72 (d, J=7.2 Hz, 1H), 7.41-7.31 (m, 2H), 7.04 (dd, J=15.6, 9.0 Hz, 1H), 6.71 (d, J=15.9 Hz, 1H), 4.15-4.11 (m, 1H); ESIMS m/z 438.8 ([M+H]⁺).

(E)-4-(4,4,4-Trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 8.00 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H), 7.47-7.44 (m, 1H), 7.02-7.01 (m, 1H), 5.10-4.90 (m, 1H).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum and the crude acid was taken on directly to the next step: ¹H NMR (300 MHz, DMSO-d₆) δ 13.65 (bs, 1H), 7.95 (s, 1H), 7.75 (d, J=7.8 Hz, 1H), 7.62-7.59 (m, 2H), 7.50 (dd, J=15.6, 9.0 Hz, 1H), 6.95 (d, J=15.9 Hz, 1H), 4.86-4.74 (m, 1H); ESIMS m/z 436.92 ([M−H]⁻); IR (thin film) 3445, 1641, 1116 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (s, 1H), 8.04 (s, 1H), 7.96 (d, J=8.4 Hz, 3H), 7.83 (d, J=8.1 Hz, 1H), 7.17-7.03 (m, 2H), 5.16-5.05 (m, 1H); ESIMS m/z 476.9 ([M−H]⁻); IR (thin film) 3436, 1651, 1116, 661 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ (300 MHz, DMSO-d₆) δ 13.4 (s, 1H), 7.99 (d, J=10.2 Hz, 3H), 7.76 (d, J=8.1 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.09-6.91 (m, 2H), 5.11-5.05 (m, 1H); ESIMS m/z 486.8 ([M−H]⁻); IR (thin film) 3436, 1651, 1115, 737 cm⁻¹.

(E)-4-(3-(4-Chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum and the crude acid was taken on directly to the next step: ¹H NMR (300 MHz, DMSO-d₆) 13.80 (bs, 1H), 8.33 (s, 1H), 7.94-7.81 (m, 5H), 7.75-7.72 (m, 1H), 7.06 (dd, J=15.9, 8.7 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H), 5.02-4.81 (m, 1H).

(E)-2-Bromo-4-(3-(4-chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) 13.50 (bs, 1H), 8.31 (s, 1H), 8.00-7.77 (m, 3H), 7.75-7.72 (m, 1H), 7.63-7.55 (m, 1H), 7.03 (dd, J=15.9, 9.0 Hz, 1H), 6.81 (d, J=15.9 Hz, 1H), 5.04-4.91 (m, 1H).; ESIMS m/z 462.16 ([M−H]⁻); IR (thin film) 3428, 1697, 1113, 749 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 7.96 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.80-7.75 (m, 1H), 7.27 (d, J=6.9 Hz, 2H), 6.96 (dd, J=15.6, 8.7 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H), 4.68-4.56 (m, 1H), 2.23 (s, 6H); ESIMS m/z 419.03 ([M−H]⁻); IR (thin film) 3445, 2928, 1713, 1146 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 7.91 (s, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.61-7.58 (m, 1H), 7.26 (d, J=6.6 Hz, 2H), 6.93 (dd, J=15.9, 8.7 Hz, 1H), 6.87 (d, J=15.9 Hz, 1H), 4.59-4.53 (m, 1H), 2.23 (s, 6H); ESIMS m/z 428.97 ([M−H]⁻); IR (thin film) 3473, 1701, 1111, 581 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.58 (bs, 1H), 7.98 (s, 1H), 7.92-7.90 (m, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.48-7.45 (m, 1H), 7.42-7.37 (m, 1H), 7.22-7.16 (m, 1H), 7.04 (dd, J=15.9, 8.7 Hz, 1H), 6.88 (d, J=15.9 Hz, 1H), 4.70-4.60 (m, 1H), 4.04-3.99 (m, 1H), 2.26 (s, 3H); ESIMS m/z 405.05 ([M−H]⁻); IR (thin film) 3437, 1710, 1145 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.39 (bs, 1H), 7.91 (s, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.61-7.58 (m 1H), 7.47-7.44 (m, 1H), 7.38-7.36 (m, 1H), 7.18 (t, J=9.6 Hz, 1H), 6.95 (dd, J=15.6, 8.7 Hz, 1H), 6.76 (d, J=15.9 Hz, 1H), 4.67-4.61 (m, 1H), 2.25 (s, 3H); ESIMS m/z 415.0 ([M−H]⁻); IR (thin film) 3435, 2989, 1700, 1260 cm⁻¹.

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown semi solid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.70 (bs, 1H), 8.01 (s, 1H), 7.91 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (J=1.6 Hz, 2H), 7.66 (t, J=3.2 Hz, 1H), 7.15 (dd, J=15.6, 9.6 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.86-4.78 (m, 1H); ESIMS m/z 491.0 ([M−H]⁻); IR (thin film) 3446, 1712, 1141, 749 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 1H), 7.70 (s, 2H), 7.65-7.64 (m, 1H), 7.56-7.52 (m, 2H), 6.94 (d, J=9.2 Hz, 1H), 6.76 (d, J=16 Hz, 1H), 4.82-4.80 (m, 1H); ESIMS m/z 500.8 ([M−H]⁻); IR (thin film) 3422, 1683, 1184, 750, 575 cm⁻¹.

(E)-4-(3-(3,4-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.5 (bs, 1H), 8.01-7.99 (m, 2H), 7.94-7.91 (m, 1H), 7.85-7.78 (m, 2H), 7.53-7.50 (m, 1H), 7.09 (dd, J=15.6, 8.7 Hz, 1H), 6.89 (d, J=15.9 Hz, 1H), 4.85-4.78 (m, 1H); ESIMS m/z 528.8 ([M−H]⁻); IR (thin film) 3437, 1722, 1168 cm⁻¹.

(E)-2-Bromo-4-(3-(3,4-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (bs, 1H), 7.98-7.96 (m, 2H), 7.84 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.63-7.61 (m, 1H), 7.51-7.49 (m, 1H), 7.01 (dd, J=15.9, 9.0 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.82-4.76 (m, 1H); ESIMS m/z 538.8 ([M−H]⁻); IR (thin film) 3446, 1699, 1166, 581 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown semi solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.01(s, 1H), 7.94 (d, J=8.7 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.63-7.55 (m, 3H), 7.41 (d, J=7.5 Hz, 1H), 7.11 (dd, J=15.6, 9.0 Hz, 1H), 6.92 (d, J=15.9 Hz, 1H), 4.89-4.82 (m, 1H); ESIMS m/z 456.98 ([M−H]⁻); IR (thin film) 3413, 1668, 1161 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.73 (s, 1H), 7.59 (m, 3H), 7.44 (s, 1H), 7.40 (d, J=7.6 Hz, 2H), 6.88 (dd, J=15.6, 9.0 Hz, 1H), 6.73 (d, J=15.9 Hz, 1H), 4.85-4.82 (m, 1H); ESIMS m/z 466.93 ([M−H]⁻); IR (thin film) 3437, 1703, 1111 cm⁻¹.

(E)-4-(3-(3-Cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.60 (bs, 1H), 8.21-8.19 (m, 1H), 8.01-7.91 (m, 3H), 7.81 (d, J=8.4 Hz, 1H), 7.12 (dd, J=15.9, 8.1 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.92-4.86 (m, 1H); ESIMS m/z 416.27 ([M−H]⁻); IR (thin film) 3429, 2238, 1713, 1116 cm⁻¹.

(E)-2-Bromo-4-(3-(3-cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.56 (bs, 1H), 8.21-8.18 (m, 1H), 8.00-7.95(m, 2H), 7.73-7.59 (m, 3H), 7.03 (dd, J=15.9, 9.3 Hz, 1H), 6.79 (d, J=15.3 Hz, 1H), 4.87-4.84 (m, 1H); ESIMS m/z 426.0 ([M−H]⁻) (E)-2-Bromo-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.4 (s, 1H), 7.96 (d, J=1.2 Hz, 1H), 7.88 (d, J=1.8 Hz, 1H), 7.74-7.68 (m, 2H), 7.63 (dd, J=8.1, 1.2 Hz, 1H), 7.57 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (dd, J=15.9, 9.3 Hz, 1H), 6.78 (dd, J=5.9 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z 451.0 ([M−H]⁻); IR (thin film) 3445, 1704, 1113, 740 cm⁻¹.

(E)-4-(3-(3-Bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.91 (s, 1H), 7.86-7.64 (m, 5H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.87 (d, J=15.9 Hz, 1H), 4.85-4.78 (m, 1H); ESIMS m/z 485.17 ([M−H]⁻); IR (thin film) 3438, 1708, 1114, 774, 516 cm⁻¹.

(E)-2-Bromo-4-(3-(3-bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (bs, 1H), 7.98 (s, 1H), 7.80-7.72 (m, 4H), 7.64-7.61 (m, 1H), 7.06 (dd, J=15.9, 9.3 Hz, 1H), 6.79 (d, J=15.6 Hz, 1H), 4.88-4.80 (m, 1H); ESIMS m/z 495.05 ([M−H]⁻); IR (thin film) 3436, 1699, 1116, 750, 531 cm⁻¹.

(E)-4-(3-(3-Bromo-5-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 8.02 (s, 1H), 7.91-7.89 (m, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.69 (s, 1H), 7.63-7.59 (m, 1H), 7.55 (d, J=9.3 Hz, 1H), 7.11 (dd, J=15.9, 9.0 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.87-4.80 (m, 1H); ESIMS m/z 469.07 ([M−H]⁻); IR (thin film) 3428, 1712, 1171, 523 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a yellow solid: ¹H NMR (400 MHz, CDCl₃) δ 8.18-8.03 (m, 2H), 7.49 (d, J=8.3 Hz, 2H), 7.42 (s, 2H), 6.66 (d, J=15.9 Hz, 1H), 6.47 (dd, J=15.9, 8.0 Hz, 1H), 4.13 (p, J=8.6 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −68.65; ESIMS m/z 409.1 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3-chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.30 (bs, 1H), 7.93 (d, J=1.2 Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.62 (dd, J=1.5, 8.1 Hz, 1H), 7.53 (s, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 6.96 (dd, J=15.6, 8.7 Hz, 1H), 6.77 (d, J=15.6 Hz, 1H), 4.73-4.61 (m, 1H), 2.35 (s, 3H); ESIMS m/z 431.77 ([M−H]⁻); IR (thin film) 3435, 1701, 1111, 750 cm⁻¹.

(E)-4-(3-(3-Chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.98 (s, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.53 (s, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.04 (dd, J=15.6, 8.4 Hz, 1H), 6.88 (d, J=15.6 Hz, 1H), 4.72-4.66 (m, 1H), 2.35 (s, 3H); ESIMS m/z 421.82 ([M−H]⁻); IR (thin film) 3460, 2926, 1712, 1170, 750 cm⁻¹.

(E)-4-(4,4,5,5,5-Pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a dark brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 8.03 (s, 1H), 7.95-7.86 (m, 3H), 7.81 (d, J=8.1 Hz, 1H), 7.16 (dd, J=15.3, 9.3 Hz, 1H), 6.92 (d, J=15.6 Hz, 1H), 4.95-4.88 (m, 1H); ¹⁹F NMR (300 MHz, DMSO-d₆) δ −80.35, −58.02; ESIMS m/z 526.8 ([M+H]⁺).

(E)-2-Bromo-4-(4,4,5,5,5-pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzoic acid

The title molecule was isolated as a dark brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 7.94 (s, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.60 (d, J=7.5 Hz 1H), 7.07 (dd, J=15.0, 8.7 Hz, 1H), 6.79 (d, J=15.6 Hz, 1H), 4.93-4.78 (m, 1H); ESIMS m/z 538.9 ([M+H]⁺); IR (thinfilm) 3420, 1602, 1123, 746 cm⁻¹.

(E)-2-Bromo-4-(3-(4-cyano-3,5-difluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ESIMS m/z 443.91 ([M−H]⁻); IR (thin film) 3447, 2244, 1703, 1114 cm⁻¹.

(E)-2-Chloro-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.39 (bs, 1H), 7.95-7.70 (m, 5H), 7.61 (d, J=8.1 Hz, 1H), 7.07 (dd, J=15.6, 9.3 Hz, 1H), 6.80 (d, J=15.6 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z 496.77 ([M−H]⁻); IR (thin film) 3439, 2920, 1707, 1165 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as an off white solid: mp 140-143° C.; ¹H NMR (400 MHz, DMSO) δ 3.60 (bs, 1H), 8.02 (s, 1H), 7.94-7.90 (m, 1H), 7.88-7.86 (m, 2H), 7.81-7.79 (m, 1H), 7.12 (dd, J=15.6, 8.8 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H), 4.86-4.81 (m, 2H); ESIMS m/z 458.88 ([M−H]⁻).

(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a light orange crystalline solid (875 mg, 88%): ¹H NMR (400 MHz, CDCl₃) δ 12.35 (s, 1H), 8.08 (d, J=8.4 Hz, 2H), 7.55-7.41 (m, 4H), 7.24 (dd, J=8.3, 2.1 Hz, 1H), 6.64 (d, J=15.8 Hz, 1H), 6.51 (dd, J=15.9, 7.7 Hz, 1H), 4.15 (p, J=8.7 Hz, 1H); ¹⁹F NMR 376 MHz, CDCl₃) δ −68.75; ESIMS m/z 375 ([M+H]⁺).

(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 13.6 (s, 1H), 8.02 (s, 1H), 7.93-7.89 (m, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.73 (d, J=8.4, Hz, 1H), 7.58 (dd, J=8.4, 2.0 Hz, 1H), 7.09 (dd, J=15.6, 8.8, Hz, 1H), 6.89 (d, J=15.6, Hz, 1H), 4.86-4.81 (m, 1H); ESIMS m/z 441.0 ([M−H]⁻); IR (thinfilm) 3447, 1710, 1169, 749 cm⁻¹.

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 7.98 (s, 1H), 7.91 (d, J=7.8 Hz 1H), 7.75-7.66 (m, 1H), 7.10 (dd, J=15.6, 9.0 Hz, 1H), 6.89 (d, J=15.9 Hz 1H), 4.86-4.80 (m, 1H); ESIMS m/z 441.1 ([M−H]⁻); IR (thinfilm) 3460, 2928, 1721, 1170, 764 cm⁻¹.

(E)-4-(3-(3,4-Dichloro-5-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a pale yellow semi solid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.58 (bs, 1H), 8.00 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (s, 1H), 7.55 (s, 1H), 7.07 (dd, J=16.4, 9.6 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H), 4.78-4.73 (m, 1H), 2.42 (s, 3H); ESIMS m/z 455.0 ([M−H]⁻); IR (thin film) 1713, 1170, 750 cm⁻¹.

(E)-2-Bromo-4-(3-(3,4-dichlorophenyl)-4,4-difluoropent-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 13.3 (s, 1H), 7.92 (s, 1H), 7.77-7.71 (m, 2H), 7.68-7.63 (m, 1H), 7.61-7.60 (m, 1H), 7.60-7.58 (m, 1H), 6.98 (dd, J=15.6, 9.2 Hz, 1H), 6.65 (d, J=15.6 Hz, 1H), 4.83-4.80 (m, 1H), 1.59-1.54 (m, 3H); ESIMS m/z 448.8 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3-chloro-5-ethylphenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.4 (bs, 1H), 7.97 (s, 2H), 7.91 (s, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.66-7.61 (m, 1H), 7.03 (dd, J=16.0, 8.4 Hz, 1H), 6.8 (d, J=15.6 Hz, 1H), 4.89-4.84 (m, 1H), 2.66-2.65 (m, 2H), 1.25 (t, J=9.2 Hz, 3H); ESIMS m/z 446.8 ([M+H]⁺).

(E)-2,6-Dimethyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.1 (s, 1H), 7.87 (s, 2H), 7.27 (s, 2H), 6.81 (dd, J=15.6, 8.7 Hz, 1H), 6.69 (d, J=15.3 Hz, 1H), 4.85-4.79 (m, 1H), 2.27 (s, 6H); ESIMS m/z 437.01 ([M−H]⁻); IR (thin film) 3285, 1621, 1162, 954 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.40 (bs, 1H), 8.07 (d, J=7.5 Hz, 1H), 7.94-7.89 (m, 2H), 7.66-7.60 (m, 2H), 7.10 (dd, J=8.7, 16.0 Hz, 1H), 6.96 (d, J=15.6 Hz, 1H), 4.82-4.80 (m, 1H); ESIMS m/z 574.7 ([M+H]⁺).

(E)-4-(3-(3,5-Dibromo-4-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.36 (bs, 1H) 8.05 (s, 2H), 7.95 (d, J=8.1 Hz, 1H), 7.87-7.67 (m, 2H), 7.14 (dd, J=9.0, 15.6 Hz, 1H), 6.96 (d, J=15.6 Hz, 1H), 4.88-4.82 (m, 1H); ESIMS m/z 564.58 ([M+H]⁺).

(E)-2-Bromo-4-(3-(4-bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.40 (bs, 1H), 7.98 (s, 1H), 7.87 (s, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.65-7.62 (m, 1H), 7.06 (dd, J=15.9, 9.3 Hz, 1H), 6.80 (d, J=15.9 Hz, 1H), 4.87-4.80 (m, 1H); ESIMS m/z 518.9 ([M−H]⁻).

(E)-4-(3-(4-Bromo-3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H) 8.03 (s, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.88 (s, 2H), 7.81 (d, J=8.1 Hz, 1H), 7.13 (dd, J=16.2, 7.5 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.89-4.83 (m, 1H); ESIMS m/z 532.0 ([M+H]⁺).

(E)-2-Bromo-4-(3-(3-chloro-4-(trifluoromethoxy)phenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 13.36 (bs, 1H) 7.95 (s, 1H), 7.73 (d, J=7.6 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.46 (s, 1H) 7.35-7.31 (m, 2H), 7.04 (dd, J=16.0, 8.8 Hz, 1H), 6.78 (d, J=16.4 Hz, 1H), 4.71-4.68 (m, 1H); ESIMS m/z 500.8 ([M−H]⁻).

Example 20 Preparation of 5-vinyl-2,3-dihydro-1H-inden-1-one (BI1)

To a stirred solution of 5-bromo-2,3-dihydro-1H-inden-1-one (5 g, 23.7 mmol) in toluene were added vinylboronic anhydride pyridine complex (8.55 g, 35.54 mmol), Pd(PPh₃)₄ (0.1 g, 0.094 mmol), K₂CO₃ (22.88 g, 165.83 mmol). The resultant reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. The residue was diluted with EtOAc and washed with water and brine. The combined organic extracts were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography (SiO₂, 5% EtOAc in petroleum ether) afforded the title compound as a solid (1.8 g, 48%): ¹H NMR (400 MHz, CDCl₃) δ 7.74 (d, J=7.2 Hz, 1H), 7.49 (br s, 1H), 7.44 (d, J=7.2 Hz, 1H), 6.82 (m, 1H), 5.90 (d, J=7.4 Hz, 1H), 5.42 (d, J=6.4 Hz, 1H), 3.20 (m, 2H), 2.70 (m, 2H); ESIMS m/z 159.06 ([M+H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 20.

6-Vinyl-3,4-dihydronaphthalen-1(2H)-one (BI2)

The product was isolated as an off-white solid (5 g, 48%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (d, J=8.4 Hz, 1H), 7.48 (m, 2H), 6.82 (m, 1H), 6.02 (d, J=7.4 Hz, 1H), 5.44 (d, J=6.4 Hz, 1H), 2.95 (m, 2H), 2.60 (m, 2H), 2.00 (m, 2H); ESIMS m/z 173.14 ([M−H]⁻); IR (thin film) 1681 cm⁻¹.

Example 21 Preparation of (E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one (BI3)

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (4 g, 11.7 mmol), 5-vinyl-2,3-dihydro-1H-inden-1-one (0.92 g, 5.8 mmol), CuCl (0.115 g, 1.171 mmol) and 2,2-bipyridyl (0.053 g, 0.34 mmol) in 1,2-dichlorobenzene (25 mL) were heated at 180° C. for 16 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 5% EtOAc in petroleum ether) to afford the title compound as a liquid (1.28 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.52 (m, 3H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 419.14 ([M+H]⁻); IR (thin film) 1708.94, 1113.60, 807.77 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 21.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-one (BI4)

The product was isolated as a brown semi-solid (1.2 g, 16%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.54 (m, 3H), 7.30 (s, 1H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 400.84 ([M−H]⁻); IR (thin film) 815, 1113, 1709 cm⁻¹.

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one (BI5)

The product was isolated as a pale yellow semi solid (1.2 g, 30%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 7.35 (m, 1H), 7.24 (m, 2H), 6.62 (d, J=16 Hz, 1H), 6.46 (m, 1H), 4.18 (m, 1H), 2.95 (m, 2H), 2.65 (m, 2H), 2.19 (m, 2H); ESIMS m/z 432.94 ([M−H]⁻); IR (thin film) 1680, 1113, 808 cm⁻¹.

Example 22 Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-one (BI6)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one (0.5 g, 1.24 mmol) in MeCN (20 mL), was added Selectfluor® (0.52 g, 1.48 mmol) and the reaction was heated to reflux temperature for 16 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and diluted with CH₂Cl₂. The solution was washed with water and brine, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in petroleum ether) to afford the title compound as a pale yellow semi solid (0.1 g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (m, 1H), 7.48 (m, 2H), 7.32 (m, 2H), 6.65 (d, J=16.0 Hz, 1H), 6.54 (dd, J=16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H); ESIMS m/z 419.06 ([M−H]⁻); IR (thin film) 1728, 1114, 817 cm⁻¹.

Example 23 Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(3,3,3-trifluoropropyl)-2,3-dihydro-1H-inden-1-amine (BC10)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one (0.15 g, 0.35 mmol) in DCE (10 mL), was added trifluoropropyl amine (0.048 g, 0.42 mmol) and NaBH₃CN (0.055 g, 0.875 mmol) in cooling and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with DCE, was washed with water and brine and dried over anhydrous Na₂SO₄. Concentration under reduced pressure gave the crude compound, which was purified by flash column chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc in petroleum ether) to afford the title compound as a colorless gummy material (0.042 g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.38-7.20 (m, 5H), 6.62 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 2H), 1.82 (m, 1H), 1.42 (m, 1H); ESIMS m/z 497.98 ([M−H]⁻); IR (thin film) 3027, 1654, 815 cm⁻¹.

Example 24 Preparation of 6-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one oxime (BI5a)

To a stirred solution of ((E)-6-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one (0.4 g, 0.92 mmol) in EtOH (50 mL) were added hydroxylamine hydrochloride (0.128 g, 1.85 mmol) and sodium acetate (NaOAc, 0.23 g, 2.77 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the crude compound, which was purified by flash column chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc in petroleum ether). The title compound was isolated as a solid (0.3 g, 73%): mp 155-158° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.41 (s, 2H), 7.24 (m, 1H), 7.17 (m, 1H), 6.57 (d, J=16 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.82 (m, 4H), 2.04 (m, 2H); ESIMS m/z 445.95 ([M−H]⁻).

Example 25 Preparation of (E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (BI5b)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one (1 g, 2.39 mmol) in MeOH (10 mL) were added ammonium acetate (NH₄OAc, 1.84 g, 23.9 mmol) and NaBH₃CN (0.44 g, 7.17 mmol,) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc. The combined organic extracts were washed with water and saturated aqueous NaHCO₃ solution, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a liquid (500 mg, crude): ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.71 (s, 2H), 4.78 (m, 1H), 4.2 (m, 1H), 2.80 (m, 1H), 2.73 (m, 1H), 1.60 (m, 2H); ESIMS m/z 419.02 ([M+H]⁺); IR (thin film) 2924, 1552, 1112, 807 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 25.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-amine (BI7)

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 401.97 ([M−H]⁻).

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-amine (BI8)

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 420.15 ([M−H]⁻).

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-1,2,3,4-tetrahydronaphthalen-1-amine (BI9)

The product was isolated as a pale yellow liquid (500 mg crude).

Example 26 Preparation of (E)-1-Methyl-3-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-enyl)-2,3-dihydro-1H-inden-1-yl)thiourea (BC1)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (0.1 g, 0.23 mmol) in Et₂O (5 mL) was added methylisothiocyanate (0.026 g, 0.35 mmol), and the mixture was stirred for 2 h at 25° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash column chromatography (SiO₂, 20% EtOAc in petroleum ether). The title compound was isolated as a liquid (65 mg, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.18 (m, 3H), 6.58 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05-2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H); ESIMS m/z 492.17 ([M+H]⁺); IR (thin film) 3211, 1569, 1113, 806 cm⁻¹.

Compounds BC2-BC3 in Table 1 were made in accordance with the procedures disclosed in Example 26.

Example 27 Preparation of (E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-yl)propanamide (BC4)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (0.1 g, 0.23 mmol) in CH₂Cl₂ (10 mL) were added trifluoropropionic acid (0.044 g, 0.34 mmol), EDC.HCl (0.038 g, 0.35 mmol), HOBt.H₂O (0.07 g, 0.46 mmol) and DIPEA (0.074 g, 0.57 mmol), and the reaction mixture was stirred for 16 h at 25° C. The reaction mixture was diluted with CH₂Cl₂ and washed with water. The combined organic layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (SiO₂, 15% EtOAc in petroleum ether) to afford the title compound as a liquid (65 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.20 (m, 3H), 6.34 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); ESIMS m/z 529.02 ([M+H]⁺); IR (thin film) 3283, 1652, 1241, 811 cm⁻¹.

Compounds BC5-BC9, BC11 in Table 1 were made in accordance with the procedures disclosed in Example 27.

Example 28 Preparation of tert-Butyl 5-vinylindoline-1-carboxylate (BI10)

Step 1. 5-Bromo-indoline (BI11)

To 5-Bromo-1H-indole (2.5 g, 12.82 mmol) in AcOH (10.0 mL), NaBH₃CN (2.38 g, 38.46 mmol) was added portion wise at 10° C. over the period of 20 min. After that the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was diluted with water and extracted with Et₂O. The organic layer was washed with saturated NaHCO₃, water and brine solution. The combined ether layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford title compound as a pale yellow semi-solid (1.8 g, 71%).

Step 2. tert-Butyl-5-bromoindoline-1-carboxylate (BI12)

To a stirred solution of 5-bromo-indoline (3.0 g, 15 mmol) in MeCN (100 ml), was added DMAP (0.185 g, 1.522 mmol) and di-tert-butyl dicarbonate (3.98 g, 18.3 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was concentrated on reduced pressure to obtain a residue which was diluted with Et₂O and washed with water and brine solution (2×). The combined ether layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as an off-white solid, which was used in the next step without further purification (3.0 g).

Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10)

A stirred solution of ten-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K₂CO₃ (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at ambient temperature. PdCl₂(dppf) (0.49 g, 0.67 mmol) was added at ambient temperature, then the reaction mixture was heated to 100° C. for 3 h. The reaction mixture was cooled to ambient temperature and filtered through a Celite® bed under vacuum and washed with Et₂O. The reaction mixture was extracted with Et₂O. The combined Et₂O layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% EtOAc/petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): mp 85.5-88.6° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).

Example 29 Preparation of (E)-tert-Butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indoline-1-carboxylate (BI13)

To a stirred solution of tert-butyl-5-vinylindoline-1-carboxylate (1.28 g, 5.23 mmol) in 1,2-dichlorobenzene (10.0 mL), was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.4 g, 10 mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g, 2.092 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 150° C. for 1 h. The reaction mixture was cooled to ambient temperature and filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as a pale yellow gummy solid (0.3 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 7.34 (d, J=6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d, J=8.4 Hz, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.21 (dd, J=16.0, 7.6 Hz, 1H), 4.07 (m, 3H), 3.10 (t, J=8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z 433.79 ([M−H]⁻); IR (thin film) 1168, 858 cm⁻¹.

Example 30 Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine (BI14)

Step 1. (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline (BI15)

To a stirred solution of (E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-carboxylate (0.2 g, 0.4 mmol) in CH₂Cl₂ (10.0 mL) was added TFA (0.6 mL) and the reaction was stirred at ambient temperature for 2 h. The reaction mixture was diluted with CH₂Cl₂, washed with saturated aq NaHCO₃, water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as a light brown gummy material which was used in the next step without further purification (0.12 g): ¹H NMR (400 MHz, CDCl₃) δ 7.33 (d, J=6.4 Hz, 2H), 7.21 (s, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.57 (d, J=8.4 Hz, 1H), 6.49 (d, J=15.6 Hz, 1H), 6.21 (dd, J=15.6, 8.4 Hz, 1H), 4.07 (m, 1H), 3.61 (t, J=8.4 Hz, 2H), 3.05 (t, J=8.4 Hz, 2H); ESIMS m/z 389.89 ([M+H]⁺); IR (thin film) 3385, 1112, 816 cm⁻¹.

Step 2. 5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline (BI16)

To (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline (0.2 g, 0.5 mmol) in concentrated HCl (5.0 ml) at 5° C., was added slowly NaNO₂ in water and the reaction was allowed to stir at ambient temperature for 2 h. The reaction mixture was diluted with CH₂Cl₂, and the CH₂Cl₂ layer washed with water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as a pale yellow solid that was used in the next step without further purification (0.2 g): ¹H NMR (400 MHz, CDCl₃) δ 7.33 (d, J=8.4 Hz, 1H), 7.39 (m, 4H), 6.61 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.4 Hz, 1H), 4.07 (m, 3H), 3.23 (t, J=8.4 Hz, 2H); ESIMS m/z 418.82 ([M+H]⁺); IR (thin film) 1488, 1112, 860 cm⁻¹.

Step 3. (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine (BI14)

To (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline (0.1 g, 0.2 mmol) in MeOH(10.0 mL) was added zinc powder (77.5 mg) and NH₄Cl (36.9 mg, 0.69 mmol) in water (2.0 mL). The reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was diluted with CH₂Cl₂ and the CH₂Cl₂ layer was washed with water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (0.08 g): ESIMS m/z 404.86 ([M+H]⁺).

Example 31 Preparation of (E)-N-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-yl)-3,3,3-trifluoropropanamide (BC12)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-amine (0.1 g, 0.247 mmol) in CH₂Cl₂ (10.0 ml) was added 3,3,3-trifluoropropanoic acid (0.038 g, 0.297 mmol), PyBOP (0.192 g, 0.370 mmol) and DIPEA (0.047 g, 0.370 mmol) and the reaction was stirred at ambient temperature for 18 h. The reaction mixture was diluted with CH₂Cl₂, and the separated CH₂Cl₂ layer dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 20-25% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (0.12 g, 33%): ¹H NMR (400 MHz, CDCl₃) δ 7.32, (d, J=6.0 Hz, 2H) 7.28 (m, 1H), 7.20 (d, J=8.0, 1H), 7.14 (d, J=8.8, 1H), 6.70 (d, J=8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); ESIMS m/z 514.86 ([M+H]⁺); IR (thin film) 3428, 1112, 857 cm⁻¹.

Example 32 Preparation of tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)

Step 1. 5-Vinyl-1H-indole (BI18)

A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs₂CO₃ (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl₂ (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through Celite® bed and washed with EtOAc. The filtrate was again extracted with EtOAc, and the combined organic layer washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M−H]⁻).

Step 2. tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)

To a stirred solution of 5-vinyl-1H-indole (0.7 g, 4.89 mmol) in MeCN (20 ml) was added DMAP (59.65 mg, 0.489 mmol) and di-tert-butyl dicarbonate (1.38 g, 6.36 mmol), and the reaction was stirred at ambient temperature for 3 h. The reaction mixture was concentrated under reduced pressure to obtain a residue which was diluted with CH₂Cl₂ and washed with water and brine solution. The combined CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as an off-white semi-solid (0.7 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 8.15 (d, J=8.0 Hz, 1H), 7.60 (s, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.59 (s, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 242.10 ([M−H]⁻); IR (thin film) 1630 cm⁻¹.

Example 33 Preparation of (E)-tert-Butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole-1-carboxylate (BI19)

To a stirred solution of tert-butyl 5-vinyl-1H-indole-1-carboxylate (0.65 g, 2.67 mmol), in 1,2-dichlorobenzene (10.0 mL) was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (1.74 g, 5.37 mmol), CuCl (53 mg, 0.537 mmol) and 2,2-bipyridyl (167 mg, 1.07 mmol). The resultant reaction mixture was degassed with argon for 30 min and heated to 150° C. for 2 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% EtOAc/petroleum ether) to afford the title compound as a light brown gummy material (0.25 g, 10%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 1.65 (s, 9H); ESIMS m/z 485.91 ([M−H]⁻); IR (thin film) 1165, 854 cm⁻¹.

Example 34 Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole (BI20)

To a stirred solution of (E)-tert-butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole-1-carboxylate (0.2 g, 0.40 mmol) in CH₂Cl₂ (10.0 mL) was added TFA (70 mg, 0.61 mmol) and the reaction was stirred at ambient temperature for 2 h. The reaction mixture was diluted with CH₂Cl₂ and washed with saturated NaHCO₃ solution, water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a light brown solid (0.2 g, 97%): mp 132.9-138.8° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.19 (br, 1H), 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (m, 1H); ESIMS m/z 387.98 ([M+H]⁺).

Example 35 Preparation of 4-Nitrophenyl 2-((tert-butoxycarbonyl)amino)acetate (BI21)

To a stirred solution of 4-nitrophenol (1.0 g, 7.19 mmol) in CH₂Cl₂ (20.0 mL) was added N-Boc glycine (1.38 g, 7.91 mmol) and EDC HCl (2.05 g, 10.785 mmol) and the reaction was stirred at ambient temperature for 24 h. The reaction mixture was diluted with CH₂Cl₂ and washed with water and saturated brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a light brown gummy material that was used in the next step without further purification (1.1 g): ¹H NMR (400 MHz, CDCl₃) δ 8.29 (d, J=9.2 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 5.07 (br, 1H), 4.20 (s, 2H), 1.47 (s, 9H); ESIMS m/z 296.27 ([M+H]⁺).

Example 36 Preparation of (E)-tert-Butyl (2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)carbamate (BI22)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole (0.1 g, 0.258 mmol) in MeCN (5.0 mL) was added 4-nitrophenyl 2-(tert-butoxycarbonylamino) acetate (0.114 g, 0.387 mmol), KF (0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol) and DIPEA (0.0332 g, 0.258 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was concentrated to obtain a residue which was diluted with CH₂Cl₂ and washed with water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a light brown gummy material which was used in the next step without further purification (0.1 g): ESIMS m/z 545.23 ([M+H]⁺).

Example 37 Preparation of (E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)

Step 1. (E)-2-Amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)ethanone (BI23)

To a stirred solution of (E)-tert-butyl 2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)-2-oxoethylcarbamate (0.05 g, 0.09 mmol) in CH₂Cl₂ (5.0 mL) was added TFA (0.01 mL) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with CH₂Cl₂ and washed with saturated NaHCO₃ solution, water and brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound which was used in the next step without further purification (50 mg).

Step 2. (E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)

To a stirred solution of (E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl) ethanone (0.04 g, 0.09 mmol) in CH₂Cl₂ (5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135 mmol) and DIPEA (29 mg, 0.225 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with CH₂Cl₂, and the CH₂Cl₂ layer was washed with water and saturated brine solution. The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO₂, 100-200 mesh; 10% EtOAc/petroleum ether) to afford the title compound as an off-white solid (30 mg, 60%): mp 121-126° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J=3.6 Hz, 3H), 6.39 (m, 1H), 4.71 (t, J=7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28 (m, 1H); ESIMS m/z 553.06 ([M−H]⁻).

Example 38 Preparation of Ethyl 2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetate (BI24)

Step 1. 5-Bromo-3-hydroxyisoindoline-1-one (BI25)

A mixture of Zn powder (1.73 g, 26.154 mmol), copper (II) sulfate pentahydrate (0.02 g, 0.08 mmol) and 2M aq NaOH (27 mL) were cooled to 0° C. 5-Bromoisoindoline-1,3-dione (5 g, 22 mmol) was added at the same temperature over the period of 30 min. The reaction mixture was stirred at 0° C. for 30 min and 3 h at ambient temperature. The reaction mixture was filtered and the filtrate was neutralized with concentrated HCl. The reaction mixture was diluted with ethanol and extracted with EtOAc. The combined EtOAc layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a brown solid, which was used in the next step without further purification (1.3 g): mp 258-261° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.03 (br, 1H), 7.81 (m, 2H), 7.69 (m, 1H), 6.44 (m, 1H), 5.88 (d, J=9.3 Hz, 1H); ESIMS m/z 225.83 ([M−H]⁻); IR (thin film) 1684, 3246, 606 cm⁻¹.

Step 2. 6-Bromophthalazine-1(2H)-one (BI26)

To a stirred solution of 5-bromo-3-hydroxyisoindoline-1-one (1.0 g, 4.40 mmol) in water, was added hydrazine hydrate (0.45 g, 8.80 mmol) and heated to 95° C. for 5 h. The reaction mixture was cooled to ambient temperature, filtered and washed with Et₂O and pentane (1:1) to afford the title compound as a white solid that was used in the next step without further purification (0.5 g): ESIMS m/z 225.15 ([M+H]⁺).

Step 3. 6-Vinylphthalazine-1(2H)-one (BI27)

A solution of 6-bromophthalazine-1(2H)-one (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K₂CO₃ (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambient temperature. PdCl₂(dppf) (0.04 g, 0.055 mmol) was added at ambient temperature, and the reaction mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to ambient temperature and filtered through Celite® bed under vacuum and washed with EtOAc. The reaction mixture was extracted with EtOAc and the combined EtOAc layer dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 50% EtOAc/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]⁺); IR (thin film) 1748, 1655, 3241 cm⁻¹.

Step 4. Ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (BI24)

To a stirred solution of 6-vinylphthalazine-1(2H)-one (0.5 g, 2.90 mmol) in DMF (5.0 mL) was added Cs₂CO₃ (0.94 g, 2.90 mmol) and the reaction was stirred for 10 min Ethyl bromoacetate (0.48 g, 2.90 mmol) was added to the reaction mixture at ambient temperature and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted and extracted with EtOAc, and the EtOAc layer was washed with water and brine solution (2×). The separated EtOAc layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 25% EtOAc/petroleum ether) to afford the title compound as a brown solid (0.34 g, 45%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.45 (m, 1H), 8.24 (m, 1H), 8.04 (m, 2H), 7.01 (m, 1H), 6.17 (d, J=2.1 Hz, 1H), 5.56 (d, J=10.8 Hz, 1H), 4.92 (s, 2H), 4.19 (m, 2H), 1.23 (m, 3H). ESIMS m/z 259.10 ([M+H]⁺); IR (thin film) 1750, 1660 cm⁻¹.

Example 39 Preparation of (E)-Ethyl 2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)acetate (BI28)

To a stirred solution of ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (0.07 g, 0.27 mmol) in 1,2-dichlorobenzene (1.0 mL) was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2fluorobenzene (0.17 g, 0.54 mmol), CuCl (0.005 g, 0.05 mmol) and 2,2-bipyridyl (0.016 g, 0.10 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 180° C. for 12 h. The reaction mixture was cooled to ambient temperature and filtered and the filtrated was concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc/petroleum ether) to afford the title compound as a brown solid (40 mg, 29%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.40 (d, J=8.4 Hz, 1H), 7.84 (d, J=1.5 Hz, 1H), 7.65 (s, 1H), 7.37 (d, J=6.3 Hz, 2H), 6.76 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz, 1H), 4.96 (s, 2H), 4.29 (m, 3H), 1.31 (t, J=7.2 Hz, 3H); ESIMS m/z 503.0 ([M+H]⁺); IR (thin film) 1660, 1114, 817 cm⁻¹.

Example 40 Preparation of (E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)acetic acid (BI29)

A solution of (E)-ethyl-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)acetate (0.04 g, 0.07 mmol) in HCl (0.5 mL) and AcOH (0.5 mL) was heated to 100° C. for 3 h. The solvent was removed under reduced pressure and the residue diluted with water. The aqueous layer was extracted with EtOAc and the separated EtOAc layer dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was triturated with Et₂O-pentane mixture to afford the title compound as a brown solid (0.03 g): ¹H NMR (400 MHz, DMSO-d₆) δ 13.0 (br s, 1H), 8.43 (m, 1H), 8.23 (d, J=8.1 Hz, 1H), 8.14 (m, 2H), 7.91 (m, 2H), 7.16 (dd, J=16.0, 8.0 Hz, 1H), 6.99 (d, J=16.0 Hz, 1H), 4.96 (m, 3H),; ESIMS m/z 473.0 ([M−H]⁻); IR (thin film) 1629, 1168, 817 cm⁻¹.

Example 41 Preparation of (E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)-N-(2,2,2-trifluoroethyl)acetamide (BC14)

To a stirred solution of (E)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)acetic acid (0.15 g, 0.31 mmol) in CH₂Cl₂ (20.0 ml) was added 2,2,2,-trifluoroethanamine (0.03 g, 0.31 mmol), PyBOP (0.17 g, 0.34 mmol) and DIPEA (0.15 ml, 0.93 mmol) at ambient temperature, and the reaction was stirred for 18 h. The reaction mixture was diluted with CH₂Cl₂ and washed with 3N HCl (2×20 mL), NaHCO₃ (2×20 mL) and brine solution (2×). The separated CH₂Cl₂ layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 20-25% EtOAc/petroleum ether) to afford the title compound as a brown solid (0.11 g): mp 172-175° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.83 (t, J=6.6 Hz, 1H), 8.42 (t, J=14.7 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.13 (t, J=6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H); ESIMS m/z 554.0 ([M−H]⁻).

Example 42 Preparation of 2-(4-Vinylbenzyl)isoindoline-1,3-dione (CI1)

To a stirred solution of 1-(chloromethyl)-4-vinylbenzene (10 g, 66 mmol) in DMF (100 mL) was added potassium phthalimide (13.3 g, 72.1 mmol), and the resultant reaction mixture was heated at 70° C. for 16 h. The reaction mixture was diluted with water and extracted with CHCl₃. The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Recrystallization from MeOH afforded the title compound as an off-white solid (8 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H), 6.65 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.21 (d, J=10.8 Hz, 1H), 4.82 (s, 2H); GCMS m/z 263.2 ([M]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

Example 43 Preparation of (E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI2)

Using the procedure of Example 10 with 2-(4-vinylbenzyl)isoindoline-1,3-dione and 1-(1-bromoethyl)-3,5-dichlorobenzene as the starting materials, the title compound was isolated as an off-white solid (0.3 g, 40-50%): mp 142-145° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42 (m, 2H), 7.36 (m, 3H), 7.27 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 488.17 ([M−H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 43.

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI3)

The title compound was isolated as an off white solid (0.3 g, 56%): mp 145-146° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42-7.31 (m, 6H), 6.58 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 522.2 ([M−H]⁻); IR (thin film) 1716, 1110, 712 cm⁻¹.

Prophetically, compounds CI4-CI5 (Table 1) could be made in accordance with the procedures disclosed in Example 43.

Example 44 Preparation of (E)-(4-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (CI6)

To a stirred solution of (E)-2-(4-(3-(3,5-dichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (1.2 g, 2.45 mmol) in EtOH was added hydrazine hydrate (0.61 g, 12 mmol), and the resultant reaction mixture was heated at 90° C. for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.9 g) which was used without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 44.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-phenyl)methanamine (CI7)

The title compound was isolated and used without further purification.

Prophetically, compounds CI8-CI9 (Table 1) could be made in accordance with the procedures disclosed in Example 44.

Example 45 Preparation of 4-(Bromomethyl)-3-chlorobenzonitrile (CI10)

To a stirred solution of 3-chloro-4-methylbenzonitrile (5 g, 25.4 mmol) in CCl₄ (50 mL) under an argon atmosphere was added NBS (5.16 g, 29 mmol), and the mixture was degassed for 30 min. To this was added AIBN (0.3 g, 1.8 mmol), and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, washed with water, and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (4.8 g, 68%): mp 87-88° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 4.60 (s, 2H); ESIMS m/z 229.77 ([M+H]⁺); IR (thin film) 2235, 752, 621 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 45.

4-(Bromomethyl)-3-(trifluoromethyl)benzonitrile (CI11)

The title compound was isolated as an off-white gummy material (5 g, 66%): ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 4.62 (s, 2H); ESIMS m/z 262.11 ([M−H]⁻); IR (thin film) 2236, 1132, 617 cm⁻¹.

3-Bromo-4-(bromomethyl)benzonitrile (CI12)

The title compound was isolated as an off-white solid (5 g, 67%): mp 82-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.61 (m, 2H), 4.62 (s, 2H); EIMS m/z 272.90; IR (thin film) 2229, 618 cm⁻¹.

4-(Bromomethyl)-3-fluorobenzonitrile (CI13)

The title compound was isolated as an off-white solid (2 g, 60%): mp 79-81° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.54 (t, J=8.0 Hz, 1H), 7.48 (dd, J=8.0 Hz, 8.0, 1H), 7.38 (dd, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 215.

Example 46 Preparation of 4-(Bromomethyl)-3-chlorobenzaldehyde (CI14)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzonitrile (4.8 g, 17 mmol) in toluene (50 mL) at 0° C. was added dropwise DIBA1-H (1.0 M solution in toluene; 23.9 mL), and the reaction mixture was stirred at 0° C. for 1 h. 10 M HCl in water (5 mL) was added until the reaction mixture turned to a white slurry and then additional 1 N HCl (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with CHCl₃. The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 80%): mp 64-66° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.00 (s, 1H), 7.92 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 4.60 (s, 2H); ESIMS m/z 232.78 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Example 46.

4-(Bromomethyl)-3-(trifluoromethyl)benzaldehyde (CI15)

The title compound was isolated as a pale yellow low-melting solid (5 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 10.09 (s, 1H), 8.19 (s, 1H), 8.09 (m, 1H), 7.81 (m, 1H), 4.61 (s, 2H); ESIMS m/z 265.04 ([M−H]⁻); IR (thin film) 1709, 1126, 649 cm⁻¹.

3-Bromo-4-(bromomethyl)benzaldehyde (CI16)

The title compound was isolated as a pale yellow solid (5 g, 62%): mp 94-95° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.96 (s, 1H), 8.05 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 4.60 (s, 2H); EIMS m/z 275.90 ([M]⁺).

4-(Bromomethyl)-3-fluorobenzaldehyde (CI17)

The title compound was isolated as an off-white solid (5 g, 61%): mp 43-45° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.1 (s, 1H), 7.54 (t, J=8 Hz, 1H), 7.48 (d, J=8 Hz, 1H), 7.38 (d, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 216 ([M]⁺).

Example 47 Preparation of 3-Chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI18)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14 mmol) in DMF (40 mL) was added potassium pthalimide (3.54 g, 19.14 mmol), and the mixture was heated at 60° C. for 6 h. The reaction mixture was cooled to ambient temperature and diluted with water (100 mL). The solid obtained was separated by filtration and dried under vacuum to afford the title compound as a white solid (2.8 g, 60%): mp 123-126° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 298.03 ([M−H]⁻).

The following compounds were made in accordance with the procedures disclosed in Example 47.

4-((1,3-Dioxoisoindolin-2-yl)-3-(trifluoromethyl)benzaldehyde (CI19)

The title compound was isolated as an off white solid (1 g, 62%): mp 142-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.15 (s, 1H), 7.91 (m, 2H), 7.80 (m, 3H), 7.27 (m, 1H), 5.19 (s, 2H); ESIMS m/z 332.03 ([M−H]⁻).

3-Bromo-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI20)

The title compound was isolated as an off-white solid (0.5 g, 64%): mp 159-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 314.00 ([M-CHO]⁻).

4-((1,3-Dioxoisoindolin-2-yl)-3-fluorobenzaldehyde (CI21)

The title compound was isolated as a white solid (2 g, 60%): mp 154-156° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 7.9 (m, 2H), 7.75 (m, 2H), 7.6 (m, 2H), 7.5 (t, J=7.6 Hz, 1H), 5.05 (s, 2H); EIMS m/z 283.1 ([M]⁺).

Example 48 Preparation of 2-(2-Chloro-4-vinylbenzyl)isoindoline-1,3-dione (CI22)

To a stirred solution of 3-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (2.8 g, 8.2 mmol) in 1,4-dioxane (30 mL) were added K₂CO₃ (1.68 g, 12.24 mmol) and methyl triphenyl phosphonium bromide (4.37 g, 12.24 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as a white solid (1.94 g, 70%): mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.70 (m, 2H), 7.41 (m, 1H), 7.21 (m, 2H), 6.71 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.23 (d, J=10.8 Hz, 1H), 4.92 (s, 2H); ESIMS m/z 298.10 ([M−H]⁻)

The following compounds were made in accordance with the procedures disclosed in Example 48.

2-(2-(Trifluoromethyl)-4-vinylbenzyl)isoindoline-1,3-dione (CI23)

The title compound was isolated as a light brown solid (0.5 g, 60%): mp 134-135° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.71 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.65 (m, 1H), 5.80 (d, J=17.8 Hz, 1H), 5.19 (d, J=10.8 Hz, 1H), 5.09 (s, 2H); ESIMS m/z 332.10 ([M+H]⁺).

2-(2-Bromo-4-vinylbenzyl)isoindoline-1,3-dione (CI24)

The title compound was isolated as an off white solid (0.5 g, 62%): mp 126-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.62 (s, 1H), 7.21 (m, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.62 (m, 1H), 5.72 (d, J=17.8 Hz, 1H), 5.15 (d, J=10.8 Hz, 1H), 4.95 (s, 2H); EIMS m/z 341.10 ([M]⁺).

2-(2-Fluoro-4-vinylbenzyl)isoindoline-1,3-dione (CI25)

The title compound was isolated as a white solid (0.5 g, 61%): mp 140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.72 (m, 2H), 7.25 (m, 1H), 7.11 (m, 2H), 6.63 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.28 (d, J=10.8 Hz, 1H), 4.92 (s, 2H); EIMS m/z 282.08.

Example 49 Preparation of (E)-2-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI26)

To a stirred solution of 2-(2-chloro-4-vinylbenzyl)isoindoline-1,3-dione (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (3.48 g, 11.36 mmol), CuCl (112 mg, 1.13 mmol) and 2,2-bipyridyl (0.35 g). The resultant reaction mixture was degassed with argon for 30 min and then was stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in n-hexane) to afford the title compound as solid (1.3 g, 50%): mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 2H), 7.24 (m, 2H), 7.20 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.10 (m, 1H); ESIMS m/z 524.07 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Example 49.

(E)-2-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI27)

The title compound was isolated as a pale white solid (0.2 g, 55%): mp 128-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 3H), 7.22 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 557.99 ([M+H]⁺).

(E)-2-(2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI28)

The title compound was isolated as an off white solid (0.2 g, 54%): mp 177-180° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 2H), 7.77 (m, 2H), 7.42 (s, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.21 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 540.08 ([M−H]⁻); IR (thin film) 1716 cm⁻¹.

(E)-2-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI29)

The title compound was isolated as an off-white solid (0.2 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 7.89 (m, 2H), 7.76 (m, 2H), 7.47 (m, 3H), 7.21 (m, 3H), 6.50 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 7.6 Hz, 1H), 4.97 (s, 2H), 4.11 (m, 1H); ESIMS m/z 522.27 ([M−H]⁻); IR (thin film) 3064, 1717, 1111, 715 cm⁻¹.

(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione (CI30)

The title compound was isolated as an off-white solid (0.2 g, 54%): mp 141-142° C.; ¹H NMR (400 MHz, CDCl₃) 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 1H), 7.38 (m, 1H), 7.24 (m, 2H), 7.19 (m, 1H), 6.60 (d, J=16.0 Hz, 1H), 6.39 (dd, J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.11 (m, 1H); ESIMS m/z 556.00 ([M−H]⁻).

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione (CI31)

The title compound was isolated as an off-white solid (0.2 g, 56%): mp 130-132° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 3H), 7.19 (m, 1H), 6.61 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.12 (m, 1H); ESIMS m/z 589.57 ([M−H]⁻).

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (CI32)

The title compound was isolated as a pale yellow solid (0.2 g, 55%): mp 160-162° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.62 (s, 1H), 7.39 (s, 2H), 7.24 (m, 1H), 7.16 (m, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.98 (s, 2H), 4.12 (m, 1H); ESIMS m/z 599.78 ([M−H]⁻).

(E)-2-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (CI33)

The title compound was isolated as an off-white solid (0.2 g, 55%): mp 72-74° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.88 (m, 2H), 7.74 (m, 2H), 7.38 (s, 2H), 7.34 (m, 1H), 7.18 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.91 (s, 2H), 4.08 (m, 1H); ESIMS m/z 539.89 ([M−H]⁻); IR (thin film) 1773 cm⁻¹.

Prophetically, compounds CI34-CI41 (Table 1) could be made in accordance with the procedures disclosed in Example 49.

Example 50 Preparation of (E)-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (CI42)

To a stirred solution of (E)-2-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (0.4 g, 0.76 mmol) in EtOH was added hydrazine hydrate (0.38 g, 7.6 mmol), and the resultant reaction mixture was heated at 80° C. for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a gummy liquid (0.3 g), which was carried on to the next step without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 50.

(E)-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI43)

The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine (CI44)

The product obtained in this reaction was carried on to the next step without further purification: ¹H NMR (400 MHz, CDCl₃) δ 7.48 (d, J=8.4 Hz, 2H), 7.39 (m, 2H), 7.23 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz, 1H), 4.12 (m, 1H), 3.90 (s, 2H); ESIMS m/z 391.90 ([M−H]⁻); IR (thin film) 3370, 3280, 1111, 817 cm⁻¹.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-phenyl)methanamine (CI45)

The title compound was isolated as a gummy material. The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine (CI46)

The title compound was isolated as a gummy material: The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI47)

The title compound was isolated as a gummy material. The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI48)

The title compound was isolated as a gummy material: ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 7.33 (t, J=7.6 Hz, 1H), 7.13 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.33 (dd, J=16.0, 7.6 Hz, 1H), 4.08 (m, 1H), 3.90 (s, 2H); ESIMS m/z 413.84 ([M+H]⁺); IR (thin film) 3368, 3274, 1114, 808 cm⁻¹.

Prophetically, compounds CI49-CI57 (Table 1) could be made in accordance with the procedures disclosed in Example 50.

Example 51 Preparation of 3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (CI58)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in N,N-dimethylacetamide (DMA; 20 mL) was added K₂CO₃ (2.36 g, 17.16 mmol) and 2-aminopyridine (0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as off-white solid (1.05 g, 50%): mp 122-123° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.94 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H), 7.4 (m, 1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s, 1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]⁺).

Example 52 Preparation of N-(2-Chloro-4-vinylbenzyl)pyridin-2-amine (CI59)

To a stirred solution of 3-chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (1 g, 4. mmol) in 1,4-dioxane (20 mL) were added K₂CO₃ (0.84 g, 6.09 mmol) and methyl triphenyl phosphonium bromide (2.17 g, 6.09 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 10% EtOAc in n-Hexane) to afford the title compound as a white solid (0.5 g, 50%): mp 119-121° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.42-7.40 (m, 3H), 7.26 (s, 1H), 6.66 (m, 2H), 6.36 (d, J=6.3 Hz, 1H), 5.75 (d, J=13.2 Hz, 1H), 4.92 (br s, 1H), 4.60 (s, 2H); ESIMS m/z 245.05 ([M+H]⁺).

Example 53 Preparation of Ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (CI60)

Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol) was added to sodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50 mL) at 0° C., and the mixture was stirred for 30 min. To this was added 5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol), and the reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was quenched with 2 N HCl solution and then stirred for 4 h at ambient temperature. The mixture was extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as a liquid (1.3 g, 20%): ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, 1H), 7.89 (s, 1H), 5.09 (s 1H), 4.23 (m, 2H), 2.27 (br s, 2H), 1.26 (m, 3H); ESIMS m/z 293.05 ([M+H]⁺); IR (thin film) 3381, 3306, 1742, 759, 523 cm⁻¹.

Example 54 Preparation of (5-Bromo-3-chloropyridin-2-yl)methanamine hydrochloride (CI61)

A stirred solution of ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (0.5 g, 1.7 mmol) in 3 N HCl (25 mL) was heated at reflux for 4 h. The reaction mixture was washed with Et₂O and water. The combined ether layer was concentrated under reduced pressure to afford the title compound as an off-white solid (400 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H), 8.70 (br s, 2H), 8.45 (s, 1H), 4.56 (m, 2H); ESIMS m/z 221.15 ([M+H]⁺).

Example 55 Preparation of 2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (CI62)

To a stirred solution of (5-bromo-3-chloropyridin-2-yl)methanamine hydrochloride (0.3 g, 1.4 mmol) in toluene (40 mL) was added TEA (0.41 g, 4.08 mmol) and phthalic anhydride (0.24 g, 1.63 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a white solid (0.25 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m, 2H), 7.74 (m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M−H]⁻); IR (thin film) 3307, 1665, 1114, 813 cm⁻¹.

Example 56 Preparation of 2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (CI63)

To a stirred solution of 2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (0.23 g, 0.65 mmol) in toluene (10 mL) were added Pd(PPh₃)₄ (3.7 mg, 0.003 mmol), K₂CO₃ (0.269 g, 1.95 mmol) and vinyl boronic anhydride pyridine complex (0.78 g, 3.28 mmol), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with water and brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as an off-white solid (0.2 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.72 (m, 1H), 6.63 (m, 1H), 5.79 (d, J=16.0 Hz, 1H), 5.39 (d, J=16.0 Hz, 1H), 5.12 (s, 2H); ESIMS m/z 299.20 ([M+H]⁺).

Example 57 Preparation of (E)-2-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichloro-phenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (CI64)

To a stirred solution of 2-((3-chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (0.35 g, 1.17 mmol) in 1,2-dichlorobenzene (10 mL) were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.8 g, 2.3 mmol), CuCl (23 mg, 0.12 mmol), 2,2-bipyridyl (0.073 g, 0.234 mmol), and the reaction mixture was heated at 180° C. for 16 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a liquid (0.4 g, 50%): mp 79-82° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.27 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.36 (s, 2H), 6.51 (d, J=15.6 Hz, 1H), 6.32 (dd, J=15.6, 8.0 Hz, 1H), 5.30 (s, 2H), 4.13 (m, 1H); ESIMS m/z 559 ([M+H]⁺).

Example 58 Preparation of (E)-(3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine (CI65)

To a stirred solution of (E)-2-((3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (200 mg, 0.358 mmol) in EtOH (5 mL) was added hydrazine hydrate (89.6 mg, 1.79 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in CH₂Cl₂. The organic layer was washed with water and brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a solid (100 mg). The product obtained in this reaction was carried on to the next step without further purification.

Example 59 Preparation of 4-(Bromomethyl)-1-naphthonitrile (CI66)

To a stirred solution of 4-methyl-1-naphthonitrile (5 g, 30 mmol) in CCl₄ (50 mL) under argon atmosphere was added NBS (6.06 g, 34.09 mmol), and the reaction mixture was degassed for 30 min AIBN (0.3 g, 2.1 mmol) was added, and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with CH₂Cl₂ (3×100 mL). The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 52%): mp 131-133° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33 (m, 1H), 8.24 (m, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.78 (m, 2H), 7.62 (d, J=8.0 Hz, 1H), 4.95 (s, 2H); ESIMS m/z 245.92 ([M+H]⁺); IR (thin film) 2217 cm⁻¹.

Example 60 Preparation of 4-(Bromomethyl)-1-naphthaldehyde (CI67)

To a stirred solution of 4-(bromomethyl)-1-naphthonitrile (8 g, 33 mmol) in toluene (100 mL) at 0° C. was added dropwise DIBAL-H (1.0 M solution in toluene; 43 mL), and the reaction mixture was stirred at 0° C. for 1 h. 3 N HCl in water (50 mL) was added to the mixture until it became a white slurry and then additional 1 N HCl (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in petroleum ether) afforded the title compound as a white solid (7 g, 88%): mp 115-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.41 (s, 1H), 9.35 (m, 1H), 8.22 (m, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.75 (m, 3H), 4.95 (s, 2H); ESIMS m/z 248.88 ([M+H]⁺).

Example 61 Preparation of 4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (CI68)

To a stirred solution of 4-(bromomethyl)-1-naphthaldehyde (7 g, 28 mmol) in DMF (100 mL) was added potassium phthalimide (7.3 g, 39.5 mmol), and the mixture was heated at 85° C. for 2 h. The reaction mixture was cooled to ambient temperature and diluted with water (100 mL). The obtained solid was separated by filtration and dried under vacuum to afford the title compound as a white solid (8.8 g, 98%): mp 190-192° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.39 (s, 1H), 9.25 (m, 1H), 8.41 (m, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.95 (m, 4H), 7.80 (m, 4H), 7.61 (m, 4H), 5.39 (s, 2H); ESIMS m/z 316.09 ([M+H]⁺); IR (thin film) 1708 cm⁻¹.

Example 62 Preparation of 2-((4-Vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (CI69)

To a stirred solution of 4-((1,3-dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (9 g, 28.5 mmol) in 1,4-dioxane (100 mL) were added K₂CO₃ (6 g, 42.8 mmol) and methyl triphenyl phosphonium bromide (15.3 g, 35.7 mmol) at ambient temperature. The reaction mixture was heated at 100° C. for 14 h and then was cooled to ambient temperature. The reaction mixture was filtered, and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (6 g, 67%): mp 146-147° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.35 (m, 2H), 7.95 (m, 4H), 7.65 (m, 4H), 7.39 (m, 1H), 5.81 (m, 1H), 5.45 (m, 1H), 5.21 (s, 2H); ESIMS m/z 314.13 ([M+H]⁺).

Example 63 Preparation of (E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione (CI70)

To a stirred solution of 2-((4-vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (1.5 g, 4.79 mmol) in 1,2-dichlorobenzene (15 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzene (3.2 g, 9.5 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95 mmol), and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 14 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (1.5 g, 56%): mp 158-160° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (m, 1H), 7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H), 7.58 (m, 2H), 7.46 (s, 2H), 7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s, 2H), 4.21 (m, 1H); ESIMS m/z 572.08 ([M−H]⁻).

Example 64 Preparation of (E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (CI71)

To a stirred solution of (E)-2-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione (0.4 g, 0.7 mmol) in EtOH was added hydrazine hydrate (0.18 g, 3.5 mmol), and the resultant reaction mixture was heated at 80° C. for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, and the solution was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The title compound was isolated as a gummy liquid (150 mg, 50%). The product obtained in this reaction was carried on to the next step without further purification.

Example 65 Preparation of 2-((4-Bromophenyl)amino)isoindoline-1,3-dione (CI72)

To a stirred solution of (4-bromophenyl)hydrazine hydrochloride (0.5 g, 2.2 mmol) in AcOH (8 mL) was added phthalic anhydride (0.398 g, 2.690 mmol), and the reaction mixture was stirred at 130° C. for 1 h under a nitrogen atmosphere. The reaction mixture was quenched with satd aqueous NaHCO₃ solution and filtered to give a solid. Purification by column chromatography (SiO₂, O-10% EtOAc in petroleum ether) afforded the title compound as a solid (60 mg, 84%): mp 205-206° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.71 (s, 1H), 7.99 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 6.79 (d, J=8.8 Hz, 2H); ESIMS m/z 314.95 ([M−H]⁻).

Example 66 Preparation of 2-((4-Vinylphenyl)amino)isoindoline-1,3-dione (CI73)

To a solution of 2-(4-bromophenylamino)isoindoline-1,3-dione (2 g, 6 mmol) in 1,2-dimethoxyethane (20 mL) and water (4 mL) were added vinyl boronic anhydride pyridine complex (4.57 g, 18.98 mmol) and K₂CO₃ (1.3 g, 9.5 mmol) followed by Pd(PPh₃)₄ (0.219 g, 0.189 mmol). The resultant reaction mixture was heated at 150° C. in a microwave for 30 min and then was concentrated under reduced pressure. Purification by column chromatography (SiO₂, 15% EtOAc in petroleum ether) afforded the title compound as a solid (200 mg, 13%): mp 174-176° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.94 (m, 4H), 7.29 (d, J=8.4 Hz, 2H), 6.72 (d, J=8.4 Hz, 2H), 6.61 (m, 1H), 5.61 (d, J=17.6 Hz, 1H), 5.05 (d, J=11.2 Hz, 1H); ESIMS m/z 263.18 ([M−H]⁻).

Example 67 Preparation of (E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)amino)isoindoline-1,3-dione (CI74)

To a stirred solution of 2-(4-vinylphenylamino)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (5 mL) were added CuCl (0.022 g, 0.273 mmol), 2,2-bipyridyl (0.07 g, 0.46 mmol) and 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.77 g, 2.27 mmol). The reaction mixture was degassed with argon for 30 min and was heated at 180° C. for 2 h. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by column chromatography (SiO₂, O-30% EtOAc in petroleum ether) to afford the title compound as a solid (450 mg, 75%): mp 187-189° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (s, 1H), 7.96 (m, 4H), 7.82 (s, 2H), 7.37 (d, J=8.8 Hz, 1H), 6.73 (d, J=8.4 Hz, 2H), 6.61 (m, 2H), 6.58 (m, 1H), 4.59 (m, 1H); ESIMS m/z 523.05 ([M−H]⁻).

Example 68 Preparation of (E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine (CI75)

To a stirred solution of (E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenylamino) isoindoline-1,3-dione (0.16 g, 0.31 mmol) in EtOH (5 mL), was added hydrazine hydrate (0.076 g, 1.52 mmol), and the reaction mixture was heated at 85° C. for 1 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure to afford the title compound as a solid (0.08 g, 66%) which was carried on to the next step without further purification.

Example 69 Preparation of 2-(4-Vinylphenoxy)isoindoline-1,3-dione (CI76)

To a stirred solution of 4-vinylphenylboronic acid (2 g, 13 mmol), 2-hydroxyisoindoline-1,3-dione (3.63 g, 24.53 mmol), and CuCl (1.214 g 12.26 mmol) in 1,2-dichloroethane (50 mL) was added pyridine (1.065 g, 13.48 mmol), and the resultant reaction mixture was stirred at ambient temperature for 48 h. The reaction mixture was diluted with water and extracted with CHCl₃. The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (2 g, 63%): mp 129-131° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.93 (d, J=2.0 Hz, 2H), 7.82 (d, J=3.2 Hz, 2H), 7.38 (d, J=2.0 Hz, 2H), 7.14 (d, J=2.0 Hz, 2H), 6.70 (m, 1H), 5.83 (d, J=16.0 Hz, 1H), 5.22 (d, J=10.8 Hz, 1H); ESIMS m/z 266.12 ([M+H]⁺).

Example 70 Preparation of (E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)isoindoline-1,3-dione (CI77)

To a stirred solution of 2-(4-vinylphenoxy)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (10 mL) was added 1-(1-bromoethyl)-3,4,5-trichlorobenzene (769 mg, 2.26 mmol), CuCl (22 mg, 0.22 mmol) and 2,2-bipyridyl (35 mg, 0.44 mmol), and the resultant reaction mixture was degassed with argon for 30 min and heated to 180° C. for 24 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in petroleum ether) to afford the title compound as a solid (0.29 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 1H), 7.62 (m, 2H), 7.50 (m, 1H), 7.40 (s, 2H), 7.12 (s, 1H), 6.90 (m, 2H), 6.60 (m, 2H), 6.20 (m, 1H), 4.08 (m, 1H); ESIMS m/z 524.09 ([M−H]⁻).

Example 71 Preparation of (E)-O-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine (CI78)

To a stirred solution of (E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenoxy)isoindoline-1,3-dione (0.2 g, 0.4 mmol) in EtOH was added hydrazine hydrate (0.1 g, 1.9 mmol), and the resultant reaction mixture was heated at 90° C. for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂. washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.08 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 6.98 (s, 1H), 6.82 (s, 2H), 6.48 (m, 1H), 6.20 (m, 1H), 5.02 (s, 1H), 4.08 (m, 1H); ESIMS m/z 394.94 ([M−H]⁻).

Example 72 Preparation of (E)-N-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzyl)acetamide (CC1)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in CH₂Cl₂ (10 mL) was added acetic anhydride (0.12 mL, 1.14 mmol), and TEA (0.217 mL, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 6 h. The reaction mixture was diluted with water and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as an off-white solid (0.2 g, 60%) mp 107-109° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, J=6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H); ESIMS m/z 402.00 ([M+H]⁺).

Compounds CC2-CC6 in Table 1 were made in accordance with the procedures disclosed in Example 72. In addition, compound DC56 in Table 1 was made from compound DC55 in accordance with the procedures disclosed in Example 72.

Example 73 Preparation of (E)-N-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)acetamide (CC7)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in DMF (5 mL) was added 2,2,2-trifluoropropanoic acid (97 mg, 0.76 mmol), HOBt.H₂O (174 mg, 1.14 mmol) and EDC.HCl (217 mg, 1.14 mmol) and DIPEA (196 mg, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; EtOAc in hexane (30-50% afforded the title compound as an off-white solid (0.2 g, 60%): mp 127-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.42 (m, 4H), 7.24 (m, 2H), 6.53 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J=6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H); ESIMS m/z 436.03 ([M+H]⁺).

Compounds CC8-CC28 in Table 1 were made in accordance with the procedures disclosed in Example 73.

Example 74 Preparation of (E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide (CC29)

Step 1: (E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)methanamine

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)methanamine (0.46 g, 1 mmol) was dissolved in MeOH (3 mL). To this was added pyridine-2-carbaldehyde (0.107 g, 1 mmol). The reaction mixture was stirred for 1 h. After 1 h, NaBH₄ (0.076 g, 2 mmol) was added and left at ambient temperature for 3 h. The reaction mixture was concentrated to give an oily residue. Purification by flash column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a pale yellow liquid (0.22 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=4.8 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 4.02 (s, 2H), 3.96 (s, 2H); ESIMS m/z 552.95 ([M+H]⁺); IR (thin film) 3338, 1114, 808 cm⁻¹.

Step 2: (E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide

(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzyl)methanamine (0.27 g, 0.05 mmol) was taken up in CH₂Cl₂ (3 mL). To this was added TEA (0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10 min After 10 min, the reaction mixture was cooled to 0° C., and cyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 h and then was washed with water and satd aq NaHCO₃ solution. The organic layer was dried over anhydrous Na₂SO₄ and evaporated to obtain pale yellow gummy material (0.15 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=4.6 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J=10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86 ([M−H]⁻); IR (thin film) 1645, 1115, 808 cm⁻¹.

Example 75 Preparation of (E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylsulfonyl)propanamide (CC30)

(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylthio)propanamide (0.15 g, 0.28 mmol) was treated with oxone (0.175 g, 0.569 mmol) in 1:1 acetone:water (20 mL) for 4 h at ambient temperature. The acetone was evaporated to obtain a white solid (0.095 g, 60%): mp 101-104° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H); ESIMS m/z 559.75 ([M−H]⁻).

Example 76 Preparation of (E)-1-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea (CC31)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1 mmol) and ethylisocyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.141 g, 60%): mp 177-178° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); ESIMS m/z 463 ([M−H]⁻).

Compounds CC32-CC35 in Table 1 were made in accordance with the procedures disclosed in Example 76.

Example 77 Preparation of (E)-3-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-1,1-dimethylurea (CC36)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1 mmol) and N,N-dimethylcarbamoyl chloride (0.08 g, 0.075 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.15 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H); ESIMS m/z 497 ([M−H]⁻); IR (thin film) 3350, 1705, 1114, 808 cm⁻¹.

Example 78 Preparation of (E)-1-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-ethylthiourea (CC37)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1 mmol) and ethyl isothicyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.14 g, 60%): mp 88-91° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.49 (d, J=8 Hz, 1H), 7.41 (d, J=7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J=16 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.0 (br s, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H); ESIMS m/z 515.01 ([M+H]⁺).

Compound CC38 in Table 1 was made in accordance with the procedures disclosed in Example 78.

Example 79 Preparation of (E)-tert-Butyl (2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea (CC39)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1 mmol) and di-tert-butyl dicarbonate (0.163 mL, 0.75 mmol), and the reaction mixture was stirred for 4 h at ambient temperature. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 10-20% EtOAc in hexane) afforded the title compound as a white solid (0.147 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H); ESIMS m/z 526.09 ([M−H]⁻); IR (thin film) 3350, 1705, 1114, 808 cm⁻¹.

Compound CC40 in Table 1 was made in accordance with the procedures disclosed in Example 79.

Example 80 Preparation of (E)-Methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)amino)-2-oxoacetate (CC41)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added TEA (0.141 mL, 1 mmol) and methyl 2-chloro-2-oxoacetate (0.09 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in hexane) afforded the title compound as a solid (0.12 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.48 (m, 1H). 7.43 (m, 3H), 7.38 (m, 1H), 7.23 (s, 1H), 6.55 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.60 (d, J=4.4 Hz, 2H), 4.18 (m, 1H), 3.85 (s, 3H); ESIMS m/z 512.22 ([M−H]⁻); IR (thin film) 1740, 1701, 1114, 808 cm⁻¹.

Example 81 Preparation of (E)-N¹-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-N²-(2,2,2-trifluoroethyl)oxalamide (CC42)

To a stirred solution of 2,2,2-trifluoroethylamine hydrochloride (0.1 g, 0.77 mmol) in CH₂Cl₂ (10 mL) was added dropwise trimethylaluminum (2 M solution in toluene; 0.39 mL, 0.77 mmol), and the reaction mixture was stirred at 25° C. for 30 min A solution of (E)-methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-benzyl)-2-oxoacetate (0.2 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added dropwise to the reaction mixture at 25° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 0.5 N HCl solution (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; 20%-40% EtOAc in n-hexane) to afford the title compound (0.13 g, 60%): mp 161-163° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (s, 1H), 7.28 (s, 1H), 6.93 (m, 1H), 6.75 (m, 1H), 4.80 (m, 1H), 4.40 (s, 2H), 3.90 (s, 2H); ESIMS m/z 578.96 ([M−H]⁻).

Example 82 Preparation of (E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)pyridin-2-amine (CC43)

To a stirred solution of N-(2-chloro-4-vinylbenzyl)pyridin-2-amine (0.3 g, 1.22 mmol) in 1,2-dichlorobenzene (5 mL) were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.83 g, 2.44 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (76 mg, 0.48 mmol). The resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as an off-white solid (0.2 g, 35%): mp 140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d, J=4.0 Hz, 1H), 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H), 4.61 (d, J=6.4 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 505.39 ([M+H]⁺).

Example 83 Preparation of (E)-N-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-en-1-yl)pyridin-2-yl)methyl)-3,3,3-trifluoropropanamide (CC44)

To a stirred solution of (E)-(3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine (0.1 g, 0.2 mmol) in CH₂Cl₂ (5 mL) were added 3,3,3-trifluoropropanoic acid (45 mg, 0.350 mmol), EDC.HCl (67 mg, 0.350 mmol), HOBt.H₂O (71 mg, 0.467 mmol) and DIPEA (60.2 mg, 0.467 mmol), and the reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with CH₂Cl₂ and washed with water. The combined CH₂Cl₂ layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in petroleum ether) afforded the title compound as a pale yellow liquid (30 mg, 35%): ¹H NMR (400 MHz, CDCl₃) δ 8.41 (s, 1H), 7.77 (s, 1H), 7.47 (br s, 1H), 7.40 (s, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.68 (d, J=4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J=10.8 Hz, 2H); ESIMS m/z 536.88 ([M−H]⁻); IR (thin film) 3320, 1674, 1114, 808. Compound CC45 in Table 1 was made in accordance with the procedures disclosed in Example 83.

Example 84 Preparation of (E)-3,3,3-Trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)propanamide (CC46)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (0.1 g, 0.22 mmol) in CH₂Cl₂ (8 mL) were added 3,3,3-trifluoropropanoic acid (0.032 g, 0.24 mmol), HOBt.H₂O (52 mg, 0.33 mmol), EDC.HCl (0.065 g, 0.33 mmol) and DIPEA (0.044 g, 0.45 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc (3×30 mL). The combined EtOAc layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as a gummy material (60 mg, 50%): mp 151-153° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H); ESIMS m/z 554.04 ([M−H]⁻).

Compounds CC47-CC48 in Table 1 were made in accordance with the procedures disclosed in Example 84.

Example 85 Preparation of (E)-1-Ethyl-3-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)urea (CC49)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (0.1 g, 0.22 mmol) in CH₂Cl₂ at 0° C. were added TEA (0.064 mL, 0.44 mmol) and ethylisocyanate (0.023 mL, 0.33 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30% EtOAc in hexane) afforded the title compound as a solid (0.07 g, 60%): mp 84-87° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.06 (m, 1H), 7.98 (m, 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J=4.6 Hz, 3H); ESIMS m/z 515.33 ([M+H]⁺).

Example 86 Preparation of (E)-N′-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)cyclopropanecarbohydrazide (CC50)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine (0.1 g, 0.3 mmol) in CH₂Cl₂ (10 mL) was added DIPEA (65 mg, 0.51 mmol), HOBt.H₂O (59 mg, 0.38 mmol), EDC.HCl (73 mg, 0.38 mmol) and cyclopropanecarbonyl chloride (0.024 g, 0.28 mmol), and the reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was diluted with satd aq NaHCO₃ solution and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 5-25% EtOAc in petroleum ether) afforded the title compound as a solid (65 mg, 55%): mp 138-140° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J=8.4 Hz, 2H), 6.65 (d, J=15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, J=15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); ESIMS m/z 461.32 ([M−H]⁻).

Compound CC51 in Table 1 was made in accordance with the procedures disclosed in Example 86.

Example 87 Preparation of (E)-N-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)cyclopropanecarboxamide (CC52)

To a stirred solution of (E)-O-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine (0.15 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added EDC.HCl (0.109 g, 0.569 mmol), HOBt.H₂O (0.087 g, 0.569 mmol), DIPEA (0.097 g, 0.758 mmol) and cyclopropanecarboxylic acid (0.049 g, 0.569 mmol). The resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with CHCl₃ (35 mL) The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 20% EtOAc in hexane) afforded the title compound as a brown liquid (0.06 g, 34%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 7.18 (s, 1H), 7.08 (s, 1H), 6.85 (m, 1H), 6.45 (m, 1H), 6.65 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.90 (m, 1H), 1.30-1.10 (m, 4H); ESIMS m/z 464.87 ([M−H]⁻).

Compound CC53 in Table 1 was made in accordance with the procedures disclosed in Example 87.

Example 88 Preparation of (Z)-3,3,3-Trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide (CC54)

A silicon borate vial was charged with (E)-3,3,3-trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide (133 mg, 0.269 mmol) and dimethyl sulfoxide (DMSO; 10 mL). The mixture was placed within 0.6 to 1 meter (m) of a bank of eight 115 watt Sylvania FR48T12/350BL/VHO/180 Fluorescent Tube Black Lights and four 115 watt Sylvania (daylight) F48T12/D/VHO Straight T12 Fluorescent Tube Lights for 72 h. The mixture was concentrated in vacuo and purified by reverse phase chromatography to give the title compound as a colorless oil (11 mg, 8%): ¹H NMR (300 MHz, CDCl₃) δ 7.28 (s, 2H), 7.25 (m, 2H), 7.10 (d, J=8.0 Hz, 2H), 6.89 (d, J=11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J=5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J=7.5 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 162.44, 137.20, 135.38, 135.23, 134.82, 134.68, 131.71, 129.00, 128.80, 128.69, 128.10, 127.96, 122.63, 76.70, 47.33 (q, J=28 Hz), 43.59, 42.12 (q, J=30 Hz); ESIMS m/z 504 ([M+H]⁺).

Compounds DC46, AC93. AC94 in Table 1 were made in accordance with the procedures disclosed in Example 88.

Example 89 Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (DI2)

The title compound was synthesized in two steps via 1-(3-chlorophenyl)-2,2,2-trifluoroethanol (DI1, prepared as in Step 1, Method B in Example 1); isolated as a colorless viscous oil (1.5 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (s, 1H), 7.42-7.35 (m, 3H), 5.02 (m, 1H), 2.65 (br s, 1H)) and Step 2 in Example 1 and isolated (0.14 g, 22%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (br s, 1H), 7.42-7.35 (m, 3H), 5.07 (m, 1H).

The following compounds were made in accordance with the procedures disclosed in Example 89.

(1-Bromo-2,2,2-trifluoroethyl)benzene (DI4)

2,2,2-Trifluoro-1-phenylethanol (DI3) was isolated (10 g, 80%): ¹H NMR (300 MHz, CDCl₃) δ 7.48 (m, 2H), 7.40 (m, 3H), 5.02 (m, 1H), 2.65 (d, J=7.1 Hz, 1H). The title compound (DI4) was isolated as a liquid (8.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q, J=7.5 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (DI20)

1-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (DI19) was isolated an off white solid: ¹H NMR (400 MHz, CDCl₃) δ 7.05 (s, 2H), 7.02 (s, 1H), 4.95 (m, 1H), 2.32 (s, 6H); ESIMS m/z 204 (ND. The title compound (DI20) was isolated (3.0 g, 51%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (DI22)

1-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (DI21) was isolated as an off white powder (5.3 g, 61%): mp 49-51° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.66 (d, 1H), 7.42-7.44 (d, 1H), 7.32-7.36 (d, 1H), 5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺). The title compound (DI22) was isolated (3.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.72 (m, 1H), 7.4-7.42 (m, 1H), 7.3-7.38 (m, 1H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (DI24)

1-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (DI23) was isolated as a pale yellow oil (5.2 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.64 (d, 1H), 7.52-7.54 (m, 1H), 7.29-7.33 (t, 1H), 5.6-5.76 (m, 1H), 2.7 (s, 1H); ESIMS m/z 243.9 ([M]⁺). The title compound (DI24) was isolated as an oil (8.7 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.71 (m, 1H), 7.44-7.52 (m, 1H), 7.27-7.3 (s, 1H), 5.81-5.91 (m, 1H).

2-(1-Bromo-2,2,2-trifluoroethyl)-1,4-dichlorobenzene (DI26)

1-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (DI25) was isolated as a yellow oil (4.1 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.7 (s, 1H), 7.3-7.37 (m, 2H), 5.51-5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺)). The title compound (DI26) was isolated (3.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.7-7.78 (m, 1H), 7.3-7.4 (m, 2H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene (DI28)

1-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI27) was isolated (3.8 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.98 (m, 3H), 5.25 (m, 1H), 3.2 (br, 1H); ESIMS m/z 312.2 ([M]⁺). The title compound (DI28) was prepared and carried on crude.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (DI30)

2,2,2-Trifluoro-1-(2,3,5-trichlorophenyl)ethanol (DI29) was isolated as a white solid (4.0 g, 60%): mp 113-115° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, 1H), 7.50 (d, 1H), 5.60-5.70 (m, 1H), 2.75 (s, 1H); ESIMS m/z 278.0 ([M]⁺). The title compound (DI30) was isolated (2.9 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.70 (d, 1H), 7.50 (d, 1H), 5.72-5.82 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene (DI32)

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI31) was isolated as a pale yellow oil (2.0 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (m, 3H), 5.08 (m, 1H), 2.81 (s, 1H); ESIMS m/z 278.1 ([M]⁺). The title compound (DI32) was isolated oil (2.0 g, 40%): ESIMS m/z 342 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-methoxybenzene (DI34)

1-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol (DI33) was isolated as an off white solid (0.8 g, 60%); mp 92-95° C.: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 3.89 (s, 3H), 2.64 (m, 1H); ESIMS m/z 274 ([M]⁺). The title compound (DI34) was isolated as a colorless liquid (0.6 g, 57%).

Example 90 Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (DI36)

The title compound was synthesized in two steps via 1-(3,5-difluorophenyl)-2,2,2-trifluoroethanol (DI35, prepared as in Step 1, Method A in Example 1; isolated as a colorless oil (0.2 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.88 (m, 1H), 5.06 (m, 1H), 2.66 (s, 1H); ESIMS m/z 212 ([M]⁺) and Step 2 in Example 1 and isolated (3.2 g, 50%); ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.86 (m, 1H), 5.03 (q, J=7.4 Hz, 1H).

The following compounds were made in accordance with the procedures disclosed in Example 90.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-chlorobenzene (DI38)

1-(4-Chlorophenyl)-2,2,2-trifluoroethanol (DI37) was isolated as a colorless oil (5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.44-7.38 (m, 4H), 5.05 (m, 1H), 2.55 (s, 1H); ESIMS m/z 210 ([M]⁺). The title compound (DI38) was isolated (3.0 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (d, J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz, 2H), 5.10 (q, J=7.2 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (DI40)

2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (DI39) was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J=8.8 Hz, 2H), 6.95 (m, J=8.8 Hz, 2H), 5.00 (m, 1H), 3.82 (s, 3H), 2.44 (s, 1H); ESIMS m/z 206.1 ([M]⁺). The title compound (DI40) was isolated (3.8 g, 62%).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-fluorobenzene (DI42)

2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol (DI41) was isolated as a colorless oil (5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.48-7.45 (m, 2H), 7.13-7.07 (m, 2H), 5.06 (m, 1H), 2.53 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI42) was prepared and carried on as crude intermediate.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (DI44)

2,2,2-Trifluoro-1-(p-tolyl)ethanol (DI43) was isolated as colorless oil (5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.37 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 5.02 (m, 1H), 2.46 (m, 1H), 2.37 (s, 3H); ESIMS m/z 190 ([M]⁺). The title compound (DI44) was isolated (3.0 g, 45%).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (DI46)

2,2,2-Trifluoro-1-(3-fluorophenyl)ethanol (DI45) was isolated as a colorless viscous oil (2.8 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 1H), 7.25 (m, 2H), 7.14 (m, 1H), 5.06 (m, 1H), 2.60 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI46) was isolated (2.0 g, 61%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (DI48)

2,2,2-Trifluoro-1-(2-fluorophenyl)ethanol (DI47) was isolated as a colorless oil (2.5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (m, 1H), 7.43 (m, 1H), 7.24 (m, 1H), 7.13 (m, 1H), 5.42 (m, 1H), 2.65 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI48) was isolated (2.0 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 7.61 (m, 1H), 7.40 (m, 1H), 7.23 (m, 1H), 7.10 (m, 1H), 5.40 (m, 1H); GCMS m/z 255 ([M−H]⁻).

Example 91 Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5)

To a stiffing solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K₂CO₃ (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with water and extracted with EtOAc (3×100 mL). The combined EtOAc layer was washed with water and brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65%): mp 145-149° C.: ¹H NMR (400 MHz, CDCl₃) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 91.

5-Formyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI49)

The title compound was isolated (2.8 g, 60%); ¹H NMR (400 MHz, CDCl₃) δ 10.10 (s, 1H), 8.98 (s, 1H), 8.35 (s, 1H), 8.30 (d, 1H), 8.22 (s, 1H), 8.07 (d, 1H); IR (thin film) 3433, 3120, 1702, 1599, 1510 cm⁻¹.

2-Chloro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI50)

The title compound was isolated as an off white solid (3.0 g, 40%): mp 149-151° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.74 (s, 1H), 8.17 (s, 1H), 8.10 (s, 1H), 7.90 (m, 2H); ESIMS m/z 208.10 ([M+H]⁺).

5-Methyl-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI51)

The title compound was isolated as a white solid (0.5 g, 74%): mp 109-111° C.; ¹H NMR (400 MHz, D₆-DMSO) δ 10.06 (s, 1H), 9.00 (s, 1H), 8.30 (s, 1H), 7.99 (s, 1H), 7.92 (d, J=9.2 Hz, 1H), 7.69 (d, J=9.2 Hz, 1H), 2.30 (s, 3H); ESIMS m/z 188.13 ([M+H]⁺).

Example 92 Preparation of 5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52)

To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K₂CO₃ (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at ambient temperature for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na₂SO₄ and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M−H]⁻); IR (thin film) 2238, 1705, 1551, 1314 cm⁻¹.

Example 93 Preparation of 4-(3-Methyl-1H-1,2,4-triazol-1-yl)benzaldehyde (DI53)

To a stirring solution of 4-fluorobenzaldehyde (5.0 g, 40.32 mmol) in DMF (50 mL), were added K₂CO₃ (3.34 g, 40.32 mmol) and 3-methyl-1,2,4-trizole (3.34 g, 40.32 mmol) and the resultant reaction mixture was stirred at ambient temperature for 4 h. After completion of the reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc (3×). The combined EtOAc layer was washed with water and brine then dried over Na₂SO₄ and concentrated under reduced pressure to afforded the title compound as a white solid (4.1 g, 60%): mp 125-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.76 (s, 1H), 8.02 (d, 2H), 7.85 (d, 2H), 2.50 (s, 3H); ESIMS m/z 188.04 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 93.

4-(1H-1,2,4-triazol-1-yl)-3-(trifluoromethyl)benzaldehyde (DI54)

The title compound was isolated as white solid (1.05 g, 60%): mp 81-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.43 (s, 1H), 8.37 (s, 1H), 8.25 (d, J=7.2 Hz, 1H), 8.18 (s, 1H), 7.79 (d, J=7.2 Hz, 1H); ESIMS m/z 241.0 ([M]⁺).

4-(3-Nitro-1H-1,2,4-triazol-1-yl)benzaldehyde (DI55)

The title compound was isolated as pale yellow solid (0.10 g, 23%): mp 159-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.10 (s, 1H), 8.89 (s, 1H), 8.15 (m, 2H), 8.00 (m, 2H); ESIMS m/z 217.11 ([M−H]⁻).

3-Bromo-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI56)

The title compound was isolated as white solid (3.2 g, 51%): mp 126-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.04 (s, 1H), 8.69 (s, 1H), 8.27 (M, 1H, 8.18 (s, 1H) 7.99 (d, J=9.2 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H); ESIMS m/z 250.9 ([M]⁺).

5-Formyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)benzonitrile (DI57)

The title compound was isolated as white solid (0.13 g, 30%): mp 147-149° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.07 (s, 1H), 8.89 (s, 1H), 8.32 (d, J=1.8 Hz, 1H), 8.24 (dd, J=8.6, 1.3 Hz, 1H), 8.06 (d, J=8.6 Hz, 1H), 2.54 (s, 3H); ESIMS m/z 213.09 ([M+H]⁺); IR (thin film) 2239, 1697 cm⁻¹.

3-Nitro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI58)

The title compound was isolated as pale yellow solid (3.0 g, 60%): mp 116-118° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.48 (s, 1H), 8.46 (s, 1H), 8.26 (d, J=6.9 Hz, 1H), 8.16 (s, 1H), 7.83 (d, J=6.9 Hz, 1H); ESIMS m/z 219.00 ([M+H]⁺).

Example 94 Preparation of 1-(4-Vinylphenyl)-1H-1,2,4-triazole (DI59)

To a stirred solution of 4-[1,2,4]-triazol-1-yl-benzaldehyde (9.0 g, 52 mmol) in 1,4-dioxane (100 mL), were added K₂CO₃ (10.76 g, 78 mmol) and methyl triphenyl phosphonium bromide (22.2 g, 62.4 mmol) at room temperature. The resultant reaction mixture was heated to 70° C. for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to room temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afforded the title compound as a white solid (5.6 g, 63%): ESIMS m/z 172.09 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 94.

1-(2-Methyl-4-vinylphenyl)-1H-1,2,4-triazole (DI60)

The title compound was isolated as an off white solid (1.5 g, 76%): ¹H NMR (400 MHz, CDCl₃) δ 8.25 (s, 1H), 8.11 (s, 1H), 7.35 (m, 2H), 7.27 (d, J=8.7 Hz, 1H), 6.74 (m, 1H), 5.82 (d, J=17.3 Hz, 1H), 5.36 (d, J=10.0 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 186.14 ([M+H]⁺).

2-(1H-1,2,4-Triazol-1-yl)-5-vinylbenzonitrile (DI61)

The title compound was isolated as an off-white solid (1.40 g, 71%): mp 126-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.76 (s, 1H), 8.18 (s, 1H), 7.82-7.84 (m, 1H), 7.72-7.80 (m, 2H), 6.70-6.80 (dd, J=17.6, 10.8 Hz, 1H), 5.90-5.95 (d, J=17.6 Hz, 1H), 5.50-5.70 (d, J=10.8 Hz, 1H); ESIMS m/z 197.03 ([M+H]⁺).

Example 95 Preparation of 2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI62)

To a stirred solution of 5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (0.36 g, 1.49 mmol) in 1,4-dioxane (25 mL), were added K₂CO₃ (0.3 g, 2.2 mmol) and methyl triphenyl phosphonium bromide (0.63 g, 1.79 mmol). The resultant reaction mixture was heated to 100° C. for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to room temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afford the title compound as a solid (0.25 g, 70%): mp 103-105° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.50 (s, 1H), 8.34 (m, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 6.87 (m, 1H), 6.20 (d, J=15.7 Hz, 1H), 5.56 (d, J=11.8 Hz, 1H); ESIMS m/z 240.27 ([M−H]⁻); IR (thin film) 2240, 1514, 1312 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 95.

1-(3-Chloro-4-vinylphenyl)-1H-1,2,4-triazole (DI63)

The title compound was isolated as an off-white solid (2.3 g, 80%): mp 134-137° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.76 (s, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.57 (d, J=9.0 Hz, 1H), 7.10 (m, 1H), 5.80 (d, J=17.2 Hz, 1H), 5.47 (d, J=12.4 Hz, 1H); ESIMS m/z 206.04 ([M+H]⁺.

3-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI64)

The title compound was isolated as a white solid (0.6 g, 60%): mp 109-111° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.42 (s, 1H), 7.40-7.60 (m, 4H), 6.70-7.00 (dd, J=17.6, 10.8 Hz, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.30 (d, J=17.6 Hz, 1H), 2.50 (s, 3H); ESIMS m/z 186.20 ([M+H]⁺).

1-(2-(Trifluoromethyl)-4-vinylphenyl)-1H-1,2,4-triazole (DI65)

The title compound was isolated as a colorless oil (0.6 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 8.32 (s, 1H), 8.14 (s, 1H), 7.84 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 6.70-6.90 (dd, J=17.6, 10.8 Hz, 1H), 5.90-6.00 (d, J=17.6 Hz, 1H), 5.50-5.80 (d, J=10.8 Hz 1H); ESIMS m/z 240.16 ([M+H]⁺).

3-Nitro-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI66)

The title compound was isolated as a pale yellow solid (61 mg, 20%): mp 137-139° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.60 (s, 1H), 7.68 (d, J=7.7 Hz, 2H), 7.60 (d, J=8.3 Hz, 2H), 6.77 (dd, J=17.7, 10.8, 1H), 5.87 (d, J=17.7 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H); ESIMS m/z 217.28 ([M+H]⁺).

1-(2-Bromo-4-vinylphenyl)-1H-1,2,4-triazole (DI67)

The title compound was isolated as a white solid (1.2 g, 40%): mp 75-77° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.48 (s, 1H), 8.12 (s, 1H), 7.75 (s, 1H) 7.42 (s, 2H), 6.70 (m, 1H), 5.83 (d, J=18 Hz, 1H), 5.42 (d, J=12 Hz, 1H); ESIMS m/z 249.1 ([M]⁺).

2-(3-Methyl-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI68)

The title compound was isolated as an off-white solid (0.6 g, 60%): mp 96-97° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66 (s, 1H), 7.80 (s, 1H), 7.74 (m, 2H), 6.73 (dd, J=17.6 Hz, 10.8 Hz, 1H), 5.88 (d, J=17.6 Hz, 1H), 5.49 (d, J=10.8 Hz, 1H), 2.52 (s, 3H); ESIMS m/z 211.10 ([M+H]⁺); IR (thin film) 2229 cm⁻¹.

1-(2-Nitro-4-vinylphenyl)-1H-1,2,4-triazole (DI69)

The title compound was isolated as a yellow solid (1.78 g, 60%): mp 102-104° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (s, 1H), 8.12 (s, 1H), 8.02 (s, 1H), 7.72-7.76 (d, J=8.0 Hz, 1H), 7.52-7.56 (d, J=17.6 Hz, 1H), 6.70-6.82 (dd, J=17.6, 10.8 Hz, 1H), 5.85-6.00 (d, J=17.6 Hz, 1H), 5.50-5.60 (d, J=10.8, Hz 1H); ESIMS m/z 217.0 ([M+H]⁺).

Example 96 Preparation of 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

Step 1. 5-Bromo-2-fluoro-3-methylbenzaldehyde

To a stirred solution of di-isopropyl amine (4.01 g, 39.88 mmol) in THF (20 mL) was added n-BuLi (1.6 M in hexane) (19.9 mL, 31.91 mmol) at −78° C. slowly dropwise over the period of 10 min, the reaction mixture was stirred at −78° C. for 30 min A solution of 4-bromo-1-fluoro-2-methylbenzene (5.0 g, 26.6 mmol) in THF (30.0 mL) was added at −78° C., and the reaction mixture was stirred for 1 h at the same temperature. DMF (5.0 mL) was added and stirred at −78° C. for another 30 min. The reaction was monitored by TLC; then the reaction mixture was quenched with 1N HCl solution (aq) at 0° C. The aqueous layer was extracted with Et₂O, washed with water and saturated brine solution. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain the crude compound purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 5% EtOAc/pet ether) to afford the title compound as a white solid (3.6 g, 64%); mp 48-50° C.: ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (dd, J=17.6, 10.8 Hz, 1H), 5.52 (d, J=17.6 Hz, 1H), 2.21 (s, 3H); ESIMS m/z 211.35 ([M−H]⁻).

Step 2. ((E)-5-Bromo-2-fluoro-3-methylbenzaldehyde oxime

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzaldehyde (3.5 g, 16.2 mmol) in ethanol (50.0 mL) were added NaOAc (2.0 g, 24.3 mmol) and hydroxylamine hydrochloride (1.69 g, 24.3 mmol) at ambient temperature. The reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was concentrated on rotavapour to obtain crude compound, which was washed with water filtered and dried under vacuum to afford the title compound as a white solid: mp 126-127° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.32 (s, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J=2.4 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 232.10 ([M+H]⁺).

Step 3. 5-Bromo-2-fluoro-3-methylbenzonitrile

A stirred solution of (E)-5-bromo-2-fluoro-3-methylbenzaldehyde oxime (0.5 g, 2.2 mmol) in acetic anhydride (5.0 mL) was heated to reflux for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound as a light brown gummy material (0.4 g, crude): ESIMS m/z 213.82 ([M+H]⁺).

Step 4. 5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI71)

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF (10.0 mL) was added K₂CO₃ (1.95 g, 14.14 mmol) followed by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) at ambient temperature. The reaction mixture was heated to 140° C. for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with EtOAc (2×100 mL). The combined EtOAc layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% EtOAc/pet ether) to afford the title compound as a pink solid (0.6 g, 49%): ¹H NMR (400 MHz, CDCl₃) δ 8.39 (s, 1H), 8.23 (s, 1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]⁺); IR (thin film) 2231, 554 cm⁻¹.

Step 5. 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

A mixture of 5-bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.6 g, 2.3 mmol), K₂CO₃ (0.95 g, 6.87 mmol), vinyl boronic anhydride (0.82 g, 3.43 mmol) and triphenylphosphine (0.13 g, 0.114 mmol) in toluene (20.0 mL) were stirred and degassed with argon for 30 min. The reaction mixture was heated to reflux for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with EtOAc (2×100 mL). The combined EtOAc layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound that was purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% EtOAc/pet ether) to afford the title compound as a pink solid (0.25 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (d, J=17.6, 1H), 5.52 (d, J=10.8 Hz, 1H), 2.21 (s, 3H), ESIMS m/z 211.35 ([M+H]⁺); IR (thin film) 2236, 1511 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Steps 4 and 5 of Example 96.

1-(2-Fluoro-4-vinylphenyl)-1H-1,2,4-triazole (DI72)

1-(4-Bromo-2-fluorophenyl)-1H-1,2,4-triazole (DI73) was isolated as a pale yellow solid (3.0 g, 75%): mp 113-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.69 (s, 1H), 8.13 (m, 2H), 7.50 (m, 1H), 7.21 (m, 1H); ESIMS m/z 241.93 ([M]⁺). The title compound (DI72) was isolated as a yellow solid (1.0 g, 71%): mp 67-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.13 (s, 1H), 7.94 (m, 1H), 7.41 (m, 1H), 7.24 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.81 (d, J=17.6 Hz, 1H), 5.37 (d, J=10.8 Hz, 1H); ESIMS m/z 190.00 ([M+H]⁺).

Example 119 Preparation of 1-(1-(4-Vinylphenyl)-1H-1,2,4-triazol-5-yl)ethanone (DI78)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]-triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C. and stirred for 30 min. To this N-methoxy-N-methyl acetamide in THF (0.66 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×50 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (280 mg, 23%): mp 97-98° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.10 (s, 1H), 7.50 (d, 2H), 7.38 (d, 2H), 6.68 (dd, 1H), 5.85 (d, 1H), 5.38 (d, 1H), 2.75 (s, 3H); ESIMS m/z 214.14 ([M+H]⁺).

Example 120 Preparation of Cyclopropyl(1-(4-vinylphenyl)-1H-1,2,4-triazol-5-yl)methanone (DI79)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]-triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C. and stirred for 30 min. To this N-methoxy N-methylcyclopropoxide in THF (0.82 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (420 mg, 30%): mp 90-91° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.50 (d, J=7.8 Hz, 2H), 7.38 (d, J=7.8 Hz, 2H), 6.75 (dd, J=16.3, 10.7 Hz, 1H), 5.81 (d, J=16.3 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 3.22 (m, 1H), 1.27 (m, 2H), 1.18 (m, 2H); ESIMS m/z 240.18 ([M+H]⁺); IR (thin film) 2922, 1630 cm⁻¹.

Example 121 Preparation of 5-(Methylthio)-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI80)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]-triazole (1 g, 5.8 mmol) in 50 mL of THF, was added n-BuLi (0.41 g, 6.4 mmol) at −78° C. and stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (0.6 g, 48%): mp 68-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.05 (m, 4H), 6.75 (dd, J=16.4, 10.7 Hz, 1H), 5.81 (d, J=16.4 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 2.73 (s, 3H); ESIMS m/z 218.09 ([M+H]⁺).

Example 122 Preparation of 5-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI81)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]-triazole (0.5 g, 2.9 mmol) in 10 mL of THF, was added n-BuLi (0.22 g, 3.5 mmol) at −78° C. and stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) afford the title compound as a pale brown liquid (250 mg, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.93 (s, 1H), 7.55 (d, J=9 Hz, 2H), 7.42 (d, J=9 Hz, 2H), 6.76 (dd, J=18, 11 Hz, 1H), 5.83 (d, J=18 Hz, 1H), 5.38 (d, J=11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13 ([M+H]⁺); IR (thin film) 1517, 1386, 1182, 847 cm⁻¹.

Example 97 Preparation of (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC1)

To a stirred solution of 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichloro-benzene (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL), were added 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (2.22 g, 13.0 mmol), CuCl (64 mg, 0.65 mmol) and 2,2-bipyridyl (0.2 g, 1.3 mmol). The resultant reaction mixture was degassed with argon for 30 min, then stirred at 180° C. for 24 h. After completion of reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the filtrate concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (0.8 g, 32%): mp 93-97° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.4 Hz, 2H), 7.38 (t, J=1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.2 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 398.05 ([M+H]⁺).

Compounds DC2-DC37, DC44, DC45, DC47-49, DC50, DC51, DC54, DC58, DC60, DC62, and DC63-DC67 in Table 1 were made in accordance with the procedures disclosed in Example 97.

Example 98 Preparation of (E)-2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile (DC40)

To a stirred solution of 2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (0.9 g, 3.7 mmol) in 1,2-dichlorobenzene (10 mL), were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.5 g, 7.5 mmol), CuCl (73 mg, 0.74 mmol) and 2,2-bipyridyl (0.23 g, 1.49 mmol) and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 14 h. After completion of the reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh, 25-30% EtOAc in Pet ether) afforded the title compound as an off white solid (0.9 g, 50%): mp 70-73° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.86 (s, 1H), 7.88 (m, 3H), 7.44 (s, 2H), 6.67 (d, J=16.0 Hz, 1H), 6.56 (dd, J=16.0, 7.6 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 436.11 ([M−H]⁻).

Example 99 Preparation of (E)-2-(3-Amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile (DC41)

To a stirred solution of (E)-2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.6 g, 1.2 mmol) in MeOH (10 mL), were added Zn dust (0.39 g, 5.98 mmol) and saturated aqueous NH₄Cl solution (5 mL) and the resultant reaction mixture was stirred at ambient temperature for 2 h. After completion of the reaction (TLC), the reaction mass was concentrated under reduced pressure. The reaction mass was diluted with CH₂Cl₂, filtered through a Celite® bed, and the obtained filtrate concentrated under reduced pressure to afford the title compound as a solid (0.5 g, 89%): mp 72-75° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J=8.4 Hz, 1H), 6.42 (dd, J=15.6, 9.2 Hz, 1H), 6.83 (d, J=15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H); ESIMS m/z 469.95 ([M−H]⁻).

Compound DC38 in Table 1 was made in accordance with the procedures disclosed in Example 99. Also, compound DC55 in Table 1 was made from compound DC54 in accordance with the procedures disclosed in Example 99, with the exception of using ammonium formate in place of NH₄Cl.

Example 100 Preparation of (E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)-N-(cyclopropanecarbonyl)cyclopropanecarboxamide (DC42)

To a stirred solution of (E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.1 g, 0.21 mmol) in CH₂Cl₂ at ambient temperature, was added cyclopropylcarbonyl chloride (0.045 g, 0.42 mmol) and the reaction mixture was stirred for 2 h at ambient temperature. The reaction mixture was diluted with CH₂Cl₂ and washed with water and brine and dried over Na₂SO₄. Concentration under reduced pressure and purification by preparative HPLC afforded the title compound as a solid (0.09 g, 79%): mp 104-107° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.78 (s, 2H), 7.83 (s, 1H), 7.80 (m, 2H), 7.42 (s, 2H), 6.65 (d, J=16.4 Hz, 1H), 6.51 (dd, J=7.6, 8.0 Hz, 1H), 4.17 (m, 1H), 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H); ESIMS m/z 609.98 ([M+H]⁺); IR (thin film) 2234, 1714, 1114, 807 cm⁻¹.

Example 101 Preparation of (E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)cyclopropanecarboxamide (DC43)

To a stirred solution of (E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.15 g, 0.31 mmol) in CH₂Cl₂ at 0° C., were added TEA (0.1 g, 1 mmol) and cyclopropylcarbonyl chloride (0.04 g, 0.38 mmol) and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂ and washed with water and brine and dried over Na₂SO₄. Concentration under reduced pressure and purification by column chromatography (SiO₂, 100-200 mesh) afforded the title compound as a solid (66 mg, 34%): mp 109-112° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.94 (br s, 1H), 8.36 (s, 1H), 8.08 (m, J=8.4 Hz, 1H), 7.91 (s, 2H), 7.84 (d, J=8.4 Hz, 1H), 7.13 (dd, J=15.6, 9.2 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H); ESIMS m/z 540.04 ([M+H]⁺); IR (thin film) 3233, 2233, 1699, 1114, 807 cm⁻¹.

Compound DC39 in Table 1 was made in accordance with the procedures disclosed in Example 101.

Example 102 Preparation of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (DI74)

To a stirred solution of 4-bromoacetophenone (10 g, 50 mmol) in DMF (100 mL), were added 1,2,4-triazole (5 g, 75 mmol), Cs₂CO₃ (32.6 g, 100.5 mmol) and CuI (1.4 g, 10.1 mmol) and the resultant reaction mixture was refluxed for 48 h. After completion of the reaction (by TLC), the reaction mixture was cooled to ambient temperature and diluted with water (200 mL) and extracted with EtOAc. The combined organic layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure. Purification by washing with Et₂O afforded the title compound as a solid (5 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 8.71 (s, 1H), 8.16, (s, 1H), 8.13 (d, J=8.6 Hz, 2H), 7.83 (d, J=8.6 Hz, 2H), 2.66 (s, 3H); ESIMS m/z 186.02 ([M−H]⁻).

Example 103 Preparation of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (DI75)

Step 1. 1-(4-(1-(Trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (DI76)

To a stirred solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (4.5 g, 24.0 mmol) in CH₂Cl₂ at 0° C., were added TEA (3.7 g, 36.1 mmol) and trimethylsilyl trifluoromethanesulfonate (8 g, 36 mmol) and the resultant reaction mixture was stirred for 1 h. The reaction mixture was quenched with a mixture of sat aqueous NaHCO₃ solution and ether. The ether layer and was separated, washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound (5.5 g) which was taken directly to next step.

Step 2. 1-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (DI75)

To a stirred solution of 1-(4-(1-(trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (6 g, 23 mmol) and 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichlorobenzene (7.1 g, 34.7 mmol) in 1,2-dichlorobenzene (30 mL) was degassed with argon. To this CuCl (0.23 g, 2.31 mmol) and 2,2-bipyridyl (0.73 g, 4.63 mmol) was added to the above reaction mixture and the resultant reaction mixture was heated to 180° C. for 18 h. After completion of the reaction (by TLC), the reaction mixture was absorbed onto silica gel and purified by column chromatography (SiO2; 10% EtOAc in petroleum ether) to afford title compound as a solid (3 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.15 (s, 1H), 8.10 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 7.33 (m, 1H), 7.30 (m, 2H), 4.20 (m, 1H), 3.63 (m, 2H); ESIMS m/z 412. 14 ([M−H]⁻).

Example 104 Preparation of 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol (DI77)

To a solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (300 mg, 0.726 mmol) in THF cooled to 0° C. was added methylmagnesium bromide (450 mg, 5 mmol) drop wise. The reaction was stirred for 3 h at 0° C., then the reaction mixture was quenched with sat aqueous NH₄Cl solution and extracted with EtOAc. The combined EtOAc layer was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (100 mg, 32%): ¹H NMR (400 MHz, CDCl₃) δ two diastereoisomers 8.58 (s, 1H, minor), 8.48 (s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H, major), 7.70 (d, J=9.0 Hz, 2H, minor), 7.53 (d, J=9.0 Hz, 2H, minor), 7.40 (d, J=9.0 Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, J=9.0 Hz, 2H, major), 7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H, major), 350 (m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H, minor); ESIMS m/z 430.05 ([M+H]⁺).

Example 105 Preparation of (E)-1-(4-(4-(3,5-Dichlorophenyl)-5,5,5-trifluoropent-2-en-2-yl)phenyl)-1H-1,2,4-triazole (DC68)

To a solution of 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol (100 mg, 0.233 mmol) in toluene was added a catalytic amount of p-toluenesulfonic acid and the water was removed by azeotropic distillation over the course of 12 h. The reaction mixture was cooled to room temperature and dissolved in EtOAc. The solution was washed with sat aqueous NaHCO₃ solution and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (30 mg, 31%).

Example 123 Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzaldehyde (DC52)

To a stirred solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.3 g, 0.71 mmol) in toluene (10 mL) at −78° C. was added dropwise diisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 0.85 mL), and the reaction mixture was stirred at −78° C. for 20 min. The reaction mixture was quenched with the addition of 1 N HCl solution, then the aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 50% EtOAc/Pet ether) to afford the title compound as a yellow oil.

Compound DC53 in Table 1 was made in accordance with the procedures disclosed in Example 123.

Example 124 Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-methyl-2-(1H-1,2,4-triazol-1-yl)aniline (DC57)

To a stirred solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)aniline (0.3 g, 0.7 mmol) in CH₂Cl₂ (10 mL) was added TEA (0.155 mL, 1.09 mmol) and methyl iodide (0.124 g, 0.873 mmol). The reaction was stirred at ambient temperature for 18 h. The CH₂Cl₂ layer was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 50% EtOAc/Pet ether) to afford the title compound as a yellow semi-solid (0.07 g, 70%).

Example 125 Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzoic acid (DC61)

A solution of (E)-ethyl 5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzoate (0.2 g, 0.4 mmol) in 6 N HCl (10 mL) was stirred at 100° C. for 18 h. The reaction was cooled to ambient temperature, resulting in a white solid precipitate. The precipitate was filtered to afford the title compound as a white solid (0.12 g, 60%).

Example 126 Preparation of (Z)-5-(E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N′-hydroxy-2-(1H-1,2,4-triazol-1-yl)benzimidamide (DC59)

A solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.3 g, 0.71 mmol), NaOAc (0.087 g, 1.065 mmol) and hydroxylammonium chloride (0.072 g, 1.065 mmol) in 9:1 ethanol/water mixture (10 mL) was stirred at 70° C. for 8 h. The reaction was cooled to ambient temperature, and the ethanol was evaporated. The residue was dissolved in water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off white solid.

Example 127 Preparation of (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC70)

Step 1. (E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one

To a solution of 1-(3,5-dichlorophenyl)ethanone (0.5 g, 2.6 mmol) in ethanol (20 mL) was added 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (0.46 g, 2.65 mmol) and the reaction was cooled to 0° C. NaOH (0.22 g, 5.29 mmol) in water (10 mL) was then added and the reaction was allowed to stir for 2 h at 0° C. The reaction was extracted with EtOAc and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound (0.149 g, 17%):); ESIMS m/z 430.05 ([M+H]⁺) 344.08

Step 2. (E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol (DC69)

To a solution of (E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one (1 g, 3 mmol) in THF (150 mL) was added trifluoromethyltrimethylsilane (0.517 g, 3.644 mmol) and tetra-n-butylammonium fluoride (TBAF) (1.0 M, 1 mL) at 0° C. The reaction was slowly warmed to ambient temperature and allowed to stir for 2 h. The reaction was then cooled to 0° C. and 5 M HCl solution was added and the reaction was stirred for an additional 4 h at ambient temperature. The reaction was extracted with CH₂Cl₂ and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 25% EtOAc/hexanes) to afford the title compound as an off-white solid (0.3 g, 25%).

Step 3. (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC70)

To a solution of (E)-4-(4-(1H-1,2,4-triazol-1-yl)-phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol (0.15 g, 0.36 mmol) in THF (5 mL) was added NaH (60%, 10 mg, 0.44 mmol) at 0° C. The reaction was allowed to stir at 0° C. for 30 min, then methyl iodide (61 mg, 0.44 mmol) was added slowly and the reaction was warmed to ambient temperature and allowed to stir for 4 h. The reaction was quenched with aqueous NH₄Cl solution and extracted with CH₂Cl₂. The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (55 mg, 35%).

Example 128 Preparation of tert-Butyl (2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)carbamate

To a stirred solution of 2-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid (4.58 g, 22.6 mmol) in methylene chloride (50 mL) was added EDC HCl (4.75 g, 24.8 mmol) followed by 2,2,2-trifluoroethylamine (2.67 g, 27.0 mmol) and DMAP (3.03 g, 24.8 mmol). The reaction mixture was stirred at ambient temperature for 18 h, then washed with aqueous 5% NaHSO₄ (2×), aqueous 10% HCl (1×) and aqueous saturated NaHCO₃ (2×). The organic phase was dried (MgSO₄) and concentrated in vacuo to afford the title compound as a white solid (2.97 g, 46%).

The following molecules were made in accordance with the procedures disclosed in Example 128:

(S)-tert-Butyl (1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 108-111° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.90 (s, 1H), 5.04 (m, 1H), 4.07 (m, 1H), 3.92 (m, 3H), 1.87 (m, 1H), 1.66 (m, 1H), 1.44 (s, 9H), 0.96 (t, J=7.4 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −72.54; ¹³C NMR (101 MHz, CDCl₃) δ 173.05, 156.04, 124.03 (q, J=278.5 Hz), 80.30, 55.56, 40.43 (q, J=34.7 Hz), 28.19, 25.63, 9.80; [α]_(D)=−33.3 (c, 10.1 mg/mL in CH₂Cl₂).

tert-Butyl (1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 113-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.36 (d, J=8.4 Hz, 1H), 5.43-5.25 (m, 1H), 4.16 (m, 1H), 3.98 (m, 1H), 3.82 (m, 1H), 1.84 (dt, J=14.0, 7.0 Hz, 1H), 1.66 (dt, J=14.2, 7.3 Hz, 1H), 1.44 (s, 9H), 0.95 (t, J=7.3 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −72.51; ¹³C NMR (101 MHz, CDCl₃) δ 172.94, 156.02, 124.47 (q, J=380.8 Hz), 80.33, 55.54, 40.46 (q, J=34.8 Hz), 28.19, 25.61, 9.79.

tert-Butyl (2-oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethyl)carbamate

The title molecule was isolated as a white solid: mp 84-88° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.89 (s, 1H), 5.44 (t, J=5.8 Hz, 1H), 4.77-4.48 (m, 1H), 3.83 (d, J=5.9 Hz, 2H), 1.45 (s, 9H), 1.33 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −77.63; ¹³C NMR (101 MHz, CDCl₃) δ 169.84, 156.33, 125.19 (q, J=280.9 Hz), 80.29, 46.20 (q, J=31.7 Hz), 44.15, 28.11, 13.88; EIMS m/z 270 ([M]⁺).

(R)-tert-Butyl (1-((2-fluoroethyl)amino)-1-oxopropan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 91-94° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.98 (bs, 1H), 6.87 (t, J=7.2 Hz, 1H), 4.47 (t, J=4.8 Hz, 1H), 4.32 (t, J=5.1 Hz, 1H), 3.97-3.92 (m, 1H), 3.41-3.37 (m, 1H), 3.33-3.28 (m, 1H), 1.37 (s, 9H), 1.16 (d, J=7.3 Hz, 3H); ESIMS m/z 235.0 ([M+H]⁺).

tert-Butyl (3-oxo-3-((2,2,2-trifluoroethyl)amino)propyl)carbamate

The title molecule was isolated as a white solid: mp 123-125° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.42-6.22 (m, 1H), 5.07 (s, 1H), 3.92 (qd, J=9.1, 6.4 Hz, 2H), 3.43 (q, J=6.2 Hz, 2H), 2.50 (t, J=6.0 Hz, 2H), 1.43 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −72.50; ¹³C NMR (101 MHz, CDCl₃) δ 171.76, 156.30, 124.02 (q, J=278.5 Hz), 79.67, 40.53 (q, J=34.8 Hz), 36.41, 36.27, 28.31.

(R)-tert-Butyl (1-(ethylamino)-1-oxopropan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 88-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.35 (s, 1H), 5.25-5.04 (m, 1H), 4.21-3.99 (m, 1H), 3.29 (dd, J=7.5, 5.9 Hz, 2H), 1.45 (s, 8H), 1.35 (d, J=7.0 Hz, 3H), 1.13 (t, J=7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 172.79, 155.51, 79.59, 49.97, 34.16, 28.25, 18.77, 14.60.

(R)-tert-Butyl (1-oxo-1-((3,3,3-trifluoropropyl)amino)propan-2-yl)carbamate

The title molecule was isolated as an off white solid: mp 101-105° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.96 (bs, 1H), 6.90 (d, J=6.9 Hz, 1H), 3.91-3.86 (m, 1H), 3.34-3.19 (m, 2H), 2.50-2.32 (m, 2H), 1.37 (s, 9H), 1.15 (d, J=7.2 Hz, 3H).

(R)-tert-Butyl (1-oxo-1-((2,2,2-trifluoroethyl)amino)pentan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 107-122° C.; ¹H NMR (400 MHz, CDCl₃)) δ 6.90 (s, 1H), 5.00 (d, J=8.0 Hz, 1H), 4.12 (d, J=7.3 Hz, 1H), 3.99-3.76 (m, 2H), 1.87-1.73 (m, 1H), 1.65-1.52 (m, 1H), 1.44 (s, 9H), 1.38 (m, 2H), 0.94 (t, J=7.3 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ rotomer −72.55, −73.27; ¹³C NMR (101 MHz, CD₃OD) δ rotomers 176.08, 157.86, minor 126.13 (q, J=279.8 Hz), major 125.83 (q, J=278.8 Hz), 80.65, 55.90, minor 42.27 (q, J=35.4 Hz), major 41.24 (q, J=35.4 Hz), 35.50, 28.73, 20.04, 14.03.

(R)-Benzyl (3-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-yl)carbamate

The title molecule was isolated as a white solid: mp 157-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.46-7.31 (m, 5H), 6.57 (d, J=8.3 Hz, 1H), 5.34 (d, J=8.9 Hz, 1H), 5.11 (s, 2H), 4.02 (dq, J=16.1, 8.8, 7.7 Hz, 2H), 3.78 (td, J=9.0, 4.7 Hz, 1H), 2.15 (q, J=6.7 Hz, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.94 (d, J=6.8 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −72.44.

Example 129 Preparation of N-(2,2,2-Trifluoroethyl) 1-amino-2-methylpropanecarboxamide hydrochloride

To tert-butyl (2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)carbamate (2.61 g, 9.18 mmol) in methylene chloride (20 mL) was added 4 M HCl in dioxane (20 mL). The solution was stirred for 6 h at ambient temperature. The reaction mixture was concentrated in vacuo to afford the title compound as a white solid (2.18 g).

The following molecules were made in accordance with the procedures disclosed in Example 129:

(R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-aminium chloride

The title molecule was isolated as a white solid: mp 210-213° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.22 (t, J=6.3 Hz, 1H), 8.37-8.27 (m, 3H), 4.07-3.95 (m, 2H), 3.95-3.84 (m, 1H), 1.38 (d, J=7.0 Hz, 3H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −70.75; lab=−6.6 (c, 5.0 mg/mL in MeOH).

1-Oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-aminium chloride

The title molecule was isolated as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 9.12 (t, J=5.7 Hz, 1H), 8.19 (s, 3H), 4.14-3.93 (m, 2H), 3.78 (t, J=6.0 Hz, 1H), 1.81-1.71 (m, 2H), 0.88 (t, J=7.2 Hz, 3H); ESIMS m/z 184.90 ([M-TFA)+H]⁺); IR (thinfilm) 3269, 1681, 1158 cm⁻¹.

2-Oxo-2-((1,1,1-trifluoropropan-2-yl)amino)ethanaminium chloride

The title molecule was isolated as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.96 (d, J=8.7 Hz, 1H), 8.09 (bs, 3H), 4.71-4.59 (m, 1H), 3.64-3.62 (m, 2H), 1.27 (d, J=6.9 Hz, 3H); EIMS m/z 170.1 ([M]⁺).

(R)-1-((2-Fluoroethyl)amino)-1-oxopropan-2-aminium chloride

The title molecule was isolated as a white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (t, J=5.1 Hz, 1H), 8.21 (bs, 3H), 4.54 (t, J=5.1 Hz, 1H), 4.38 (t, J=4.8 Hz, 1H), 3.85-3.79 (m, 1H), 3.50-3.45 (m, 1H), 3.41-3.36 (m, 1H), 1.36 (d, J=7.2 Hz, 3H); ESIMS m/z 135.1 ([M+H]⁺); IR (thinfilm) 3331, 2983, 1660, 1161, 597 cm⁻¹.

3-Oxo-3-((2,2,2-trifluoroethyl)amino)propan-1-aminium chloride

The title molecule was isolated as a white solid: mp 193-197° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 8.94 (t, J=6.4 Hz, 1H), 8.16 (s, 3H), 3.99-3.79 (m, 2H), 2.98 (t, J=7.3 Hz, 2H), 2.64 (t, J=7.3 Hz, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −70.74.

(R)-1-(Ethylamino)-1-oxopropan-2-aminium chloride

The title molecule was isolated as a white solid: mp 223-236° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 8.65 (t, J=5.4 Hz, 1H), 8.32 (s, 3H), 3.89-3.66 (m, 1H), 3.12 (p, J=7.0 Hz, 2H), 1.35 (d, J=6.9 Hz, 3H), 1.05 (t, J=7.2 Hz, 3H); ¹³C NMR (101 MHz, DMSO-d₆) δ 168.98, 48.08, 33.54, 17.16, 14.43.

(R)-1-Oxo-1-((3,3,3-trifluoropropyl)amino)propan-2-aminium chloride

The title molecule was isolated as an off white solid: mp 128-131° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.62 (bs, 1H), 8.10 (bs, 3H), 3.82-3.79 (m, 1H), 3.50-3.38 (m, 2H), 2.50-2.37 (m, 2H), 1.34 (d, J=6.9 Hz, 3H).

(R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)pentan-2-aminium chloride

The title molecule was isolated as a white solid: mp 204-210° C.; ¹H NMR (400 MHz, CD₃OD) δ 4.17-4.00 (m, 1H), 3.98-3.69 (m, 2H), 1.83 (dt, J=15.0, 7.5 Hz, 2H), 1.50-1.35 (m, 2H), 0.99 (t, J=7.3 Hz, 3H); ¹⁹F NMR (376 MHz, CD₃OD) δ −73.90; ¹³C NMR (101 MHz, CD₃OD) δ 170.97, 125.72 (q, J=277.9 Hz), 54.37, 41.30 (q, J=34.7 Hz), 34.65, 19.00, 13.94.

Example 130 Preparation of (R)-tert-Butyl 1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate

To a stirred solution of (R)-tert-butyl 1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate (100 mg, 0.37 mmol) in CH₂Cl₂ (10 mL) was added P₂S₅ (24 mg, 0.11 mmol) and hexamethyldisiloxane (HMDO) (0.13 mL, 0.59 mmol) at room temperature and the mixture was refluxed for 3 h. The reaction mixture was cooled to room temperature and another portion of P₂S₅ (24 mg, 0.11 mmol) was added and the resulting mixture was refluxed for 18 h. The volatiles were evaporated, pentane (25 mL) was added to the residue and stirred for 10-15 min. The pentane layer was decanted, concentrated in vacuo and the residue was passed through a short silica pad eluting with pentane followed by CH₂Cl₂ to give the title compound as colorless liquid (30 mg, 30%): ¹H NMR (400 MHz, DMSO-d₆) δ 10.27 (t, J=5.4 Hz, 1H), 7.00 (d, J=6.8 Hz, 1H), 4.57-4.35 (m, 3H), 1.32 (s, 9H), 1.25 (d, J=7.6 Hz, 3H); ESIMS m/z 286.2 ([M+H]⁺); IR (thin film) 3233, 1683, 1257 cm⁻¹.

Example 131 Preparation of (R)-1-Thioxo-1-((2,2,2-trifluoroethyl)amino)propan-2-aminium 2,2,2-trifluoroacetate

To a stirred solution of (R)-tert-butyl 1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-ylcarbamate (200 mg, 0.69 mmol) in CH₂Cl₂ (5 mL) was added TFA (0.5 mL) dropwise and the reaction mixture was stirred for 18 h. The volatiles were evaporated and the residue was triturated with pentane to give the title compound as colorless gum, which was taken to next step without further purification (200 mg): ¹H NMR (300 MHz, DMSO-d₆) δ 10.99 (bs, 1H), 8.23 (bs, 2H), 4.62-4.55 (m, 2H), 4.23-4.19 (m, 1H), 1.43 (d, J=8.4 Hz, 3H); ESIMS m/z 186.2 ([M+H]⁺); IR (thin film) 3445, 2967, 1168 cm⁻¹.

The following molecule was made in accordance with the procedures disclosed in Example 131:

(S)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)butan-2-aminium 2,2,2-trifluoroacetate

The title molecule was isolated as a colorless gum: ¹H NMR (300 MHz, DMSO-d₆) δ 9.12 (t, J=5.7 Hz, 1H), 8.19 (bs, 2H), 4.14-3.93 (m, 2H), 3.80 (t, J=6.0 Hz, 1H), 1.81-1.71 (m, 2H), 0.88 (t, J=7.2 Hz, 3H); ESIMS m/z 185.00 ([M+H]⁺); IR (thin film) 3459, 1674, 1169 cm⁻¹.

Example 132 Preparation of 2-Bromo-N—((S)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F10 and F11)

The title molecule was prepared as described in Example 15. The diastereomeric pairs were separated by chiral HPLC using Chiralpak® IA (4.6×250 mm) 5 m column using 0.1% TFA in hexane and isopropanol as the mobile phase (isocratic 70:30) with a flow rate 1.0 mL/min at ambient temperature. Diastereomer F10 was collected at a retention time of 4.55 min and possessed an optical rotation of [α]_(D) ³⁰=+35.6 (c, 0.5% in CH₂Cl₂). Diastereomer F11 was collected at 8.71 min and possessed an optical rotation of [α]_(D) ³⁰=−82.0 (c, 0.5% in CH₂Cl₂). Characterization data for these molecules are listed in Table 2.

Example 133 Preparation of 2-Bromo-N—((R)-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F12 and F13)

The title molecule was prepared as described in Example 15. The diastereomeric pairs were separated by chiral HPLC using Chiralpak® IA (4.6×250 mm) 5 μm column using 0.1% TFA in hexane and isopropanol as the mobile phase (isocratic 70:30) with a flow rate 1.0 mL/min at ambient temperature. Diastereomer F12 was collected at a retention time of 5.62 min and possessed an optical rotation of [α]_(D) ³⁰=+59.4 (c, 1% in CH₂Cl₂). Diastereomer F13 was collected at 8.85 min and possessed an optical rotation of [α]_(D) ³⁰=−44.0 (c, 1% in CH₂Cl₂). Characterization data for these molecules are listed in Table 2.

The following molecules was prepared in accordance with the procedures disclosed in Example 133:

N—((R)-1-Oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide (F20A and F20B)

Diastereomer F20A (isomer 1) was collected at a retention time of 4.13 min and possessed an optical rotation of [α]_(D) ²⁵=+49.2 (c, 1.0% in CH₂Cl₂). Diastereomer F20B was collected at 4.88 min and possessed an optical rotation of [α]_(D) ²⁵=−38.8 (c, 1.0% in CH₂Cl₂). Characterization data for these molecules are listed in Table 2.

F20A and F20B Stereochemical Assignment

F20A and F20B were dissolved in CDCl₃ and placed in a 100 μm path length cell with BaF₂ windows. IR and vibrational circular dichroism (VCD) spectra were recorded on a IR-2×TM VCD spectrometer (BioTools, Inc.) equipped with dual PEM accessory, with 4 cm⁻¹ resolution. The sample and CDCl₃ spectra were acquired for 21 h on an instrument optimized at 1400 cm⁻¹. The solvent-subtracted IR and VCD spectra were collected.

Theoretical Calculations: F20 with R,R- and S,R-configurations were built with Maestro (Schrodinger, LLC. New York, N.Y.). The conformational search was carried out with MacroModel (Schrodinger, LLC. New York, N.Y.) with MMFF94x force field to generate low-energy conformers. Single point calculation (SPE), geometry, frequency, and IR and VCD calculations were performed at the DFT level (B3LYP/lacvp**) in Jaguar (Schrodinger, LLC. New York, N.Y.). A scaling factor of 0.96 was applied to the frequency calculation. Analysis: for F20 with R,R- and S,R-configurations, the top 100 low-energy conformers generated with MacroModel were selected for DFT SPE calculations. These calculations resulted in the 8 and 4 conformers that have energies within 1 kcal/mol higher than the lowest energy conformer for R,R- and S,R-configurations, respectively. The frequency calculations were performed on these conformers to determine the IR and VCD spectra. The Boltzmann-weighted IR and VCD spectra of these conformers were compared with the observed IR and VCD spectra. Based on the overall agreement in VCD pattern between the observed and calculated spectra, the absolute configuration of F20A is assigned as R,R-configuration. The assignment was evaluated by CompareVOA program (BioTools). The confidence level of the assignment is 88% based on a database that includes 105 previous correct assignments for different chiral structures. However, the observed spectrum for F20B does not agree well with the calculated spectrum for S,R-configuration with a confidence level of 65%. But considering that the compound has only one chiral center, two possible configurations and F20A is of R,R-configuration, F20B can be with high confidence assigned as the S,R-configuration.

Example 134 Preparation of (E)-2-Methyl-N-(2-methyl-1-thioxo-1-(2,2,2-trifluoroethylamino)propan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzothioamide (F31)

To a stirred solution of (E)-2-methyl-N-(2-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (400 mg, 0.68 mmol) in CH₂Cl₂ (50 mL) was added P₂₅₅ (75 mg, 0.34 mmol) and HMDO (0.25 mL, 1.12 mmol) at room temperature and the mixture was refluxed for 3 h. The reaction mixture was cooled to room temperature and another portion of P₂₅₅ (75 mg, 0.34 mmol) was added and the resulting mixture was refluxed for 18 h. The volatiles were evaporated and the residue was purified by prep TLC to give the title compound as pale yellow gum (47 mg, 11%). Characterization data for this molecule is listed in Table 2.

Example 135 Preparation of (E)-2-Bromo-N-(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F1)

To (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (200 mg, 0.409 mmol) in MeCN (5 mL) was added 1H-benzo[d][1,2,3]-triazol-1-ol hydrate (63 mg, 0.411 mmol), HBTU (155 mg, 0.409 mmol), N-(2,2,2-trifluoroethyl) 1-amino-2-methyl-propanecarboxamide hydrochloride (180 mg, 0.816 mmol) and diisopropylethylamine (0.24 mL, 1.38 mmol). After 24 h the material was concentrated in vacuo. The crude product was purified by passing the crude reaction mixture through a silica frit and eluting with EtOAc/hexane (1:2). The recovered material was further purified by medium pressure chromatography on silica with EtOAc/hexane as the eluent to afford the title as a white foam (147 mg, 55%). Characterization data for this molecule is listed in Table 2.

Example 136 Preparation of 1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanone

Isopropyl magnesium chloride lithium chloride complex (22.0 mL, 28.02 mmol) was added dropwise to a stirred solution of 5-bromo-1,3-difluoro-2-methoxybenzene (5.0 g, 22.42 mmol) at −5° C. in THF (100 mL) and the reaction mixture was stirred at same temperature for 30 min. Methyl trifluoroacetate (3.67 g, 28.69 mmol) was added dropwise and the reaction mixture was stirred at ambient temperature for 2 h. A 2 N HCl solution (200 mL) was added to quench the reaction and then it was extracted with diethylether. The combined organic layers were washed with brine, dried (Na₂SO₄) filtered and concentrated to afford the title compound (5.4 g, crude) as a yellow liquid. The material was taken to next step without further purification. ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.60 (m, 2H) 4.19 (s, 3H); ESIMS m/z 240.1 ([M]⁺).

The following molecule was prepared in accordance with the procedures disclosed in Example 136:

2,6-Difluoro-4-(2,2,2-trifluoroacetyl)benzonitrile

¹H NMR (400 MHz, CDCl₃) δ 7.45 (d, J=8.4 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H).; EIMS m/z 235.1 ([M]⁺).

Example 137 Preparation of (E)-N-(1-((2-Fluoroethyl)amino)-1-oxopropan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide (P1618A)

Step 1: (2R)-tert-Butyl 2-(4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzamido)propanoate

The title compound was prepared according to procedures outlined in Example 15: ¹HNMR (400 MHz, DMSO d₆) δ 8.73 (d, J=6.8 Hz, 1H), 7.92-7.90 (m, 3H), 7.61 (d, J=7.2 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 6.99 (dd, J=15.2, 9.2 Hz, 1H), 6.77 (d, J=15.2 Hz, 1H), 4.85-4.80 (m, 1H), 4.30-4.26 (m, 1H), 1.43 (s, 9H), 1.33 (d, J=6.8 Hz, 3H); ESIMS m/z 601.9 ([M−H]⁻); IR (KBr) 3414, 1732, 1661, 1170, 748 cm⁻¹.

Step 2: (2R)-(4-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzamido)propanoic acid

TFA (1 mL) was added to a stirred solution of tert-butyl 2-(2-bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)propanoate (1.0 g, 1.63 mmol) in CH₂Cl₂ (20 mL) at 0° C. and the reaction mixture was stirred at ambient temperature for 18 h. The volatiles were evaporated under vacuum and the residue was triturated with pentane to afford the title compound as brown solid (0.65 g, 67%): ¹HNMR (400 MHz, DMSO-d₆) δ 12.60 (bs, 1H), 8.82 (d, J=8.0 Hz, 1H), 7.99 (s, 1H), 7.92-7.89 (m, 3H), 7.51 (d, J=8.0 Hz, 1H), 7.08 (dd, J=15.6, 8.8 Hz, 1H), 6.88 (d, J=15.6 Hz, 1H), 4.88-4.83 (m, 1H), 4.41-4.34 (m, 1H), 1.34 (d, J=7.2 Hz, 3H); ESIMS: m/z 545.7 ([M−H]⁺); IR (KBr) 3410, 3281, 2928, 1728, 1172, 744 cm⁻¹.

Step 3. (E)-N-(1-((2-Fluoroethyl)amino)-1-oxopropan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide (P1618)

DIPEA (0.60 mL, 1.08 mmol), PyBOP (180 mg, 0.36 mmol) 2-(4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzamido)propanoic acid (35 mg, 0.36 mmol) were added to a stirred solution of compound 1 (200 mg, 0.36 mmol) in CH₂Cl₂ (10 mL) at ambient temperature and the reaction mixture was stirred for 18 h. The reaction mixture was diluted CH₂Cl₂, washed with 1N HCl, followed by a saturated NaHCO₃ solution, water and brine. The organic phase was dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 10% EtOAc in petroleum ether to afford the title compound as a brown solid (85 mg, 39%).

The following molecule was prepared in accordance with the procedures disclosed in Example 137, Step 1:

tert-Butyl 2-(2-bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)propanoate

¹H NMR (400 MHz, DMSO-d₆): δ 8.82 (d, J=7.6 Hz, 1H), 7.99 (s, 1H), 7.91-7.90 (m, 3H), 7.50 (d, J=7.6 Hz, 1H), 7.07 (dd, J=16.0, 8.8 Hz, 1H), 6.88 (d, J=15.2 Hz, 1H), 4.88-4.83 (m, 1H), 4.31-4.27 (m, 1H), 1.42 (s, 9H), 1.32 (d, J=7.6 Hz, 3H); ESIMS m/z 611.7 ([M−H]⁻); IR (KBr) 3296, 2932, 1732, 1162, 743, 556 cm⁻¹.

(E)-tert-Butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetate

Isolated as a (620 mg, 72%) pale yellow solid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.77 (t, J=6.0 Hz, 1H), 7.93-7.91 (m, 3H), 7.62 (d, J=6.8 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.00 (dd, J=15.6, 9.2 Hz, 1H), 6.77 (d, J=16.0 Hz, 1H), 4.86-4.81 (m, 1H), 3.86-3.85 (m, 2H), 1.33 (s, 9H). ESIMS m/z 599.87 ([M+H]⁺).

The following molecule was prepared in accordance with the procedures disclosed in Example 137, Step 2:

2-(2-Bromo-4-((E)-4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)propanoic acid

¹HNMR (400 MHz, DMSO-d₆): δ 12.62 (bs, 1H), 8.73 (d, J=9.6 Hz, 1H), 7.93-7.91 (m, 3H), 7.61 (d, J=8.1 Hz, 1H), 7.37 (d, J=7.8 Hz, 1H), 7.01 (dd, J=15.6, 9.0 Hz, 1H), 6.78 (d, J=15.9 Hz, 1H), 4.89-4.79 (m, 1H), 4.42-4.32 (m, 1H), 1.36 (d, J=7.2 Hz, 3H); ESIMS: m/z 558.0 ([M+H]⁺); IR (KBr) 3418, 1650, 1115, 747, 560 cm⁻¹.

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetic acid

Isolated as an (550 mg, 97%) off white solid. ¹H NMR (300 MHz, DMSO-d6) δ 12.56 (bs, 1H), 8.73 (t, J=5.4 Hz, 1H), 7.93-7.91 (m, 3H), 7.62 (d, J=9.3 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H), 7.01 (dd, J=15.9, 9.0 Hz, 1H), 6.78 (d, J=15.9 Hz, 1H), 4.89-4.80 (m, 1H), 3.90-3.88 (m, 2H). ESIMS m/z 541.82 ([M−H]⁻).

Example 138 Preparation of (E)-2-Chloro-5-hydroxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

Step 1. Methyl 4-bromo-2-chloro-5-methoxybenzoate

A 25 mL round bottomed flask equipped with a magnetic stir bar was charged with 4-bromo-2-chloro-5-methoxybenzoic acid (JACS, 1963, 730-2; 1.25 g, 4.72 mmol), 20% MeOH/EtOAc (25 mL) and cooled in an ice-water bath. Trimethylsilyldiazomethane (TMSCHN₂ 2 M in hexanes, 2.6 mL, 5.20 mmol) was added dropwise via an addition funnel. The reaction continued to stir for 1 h then it was concentrated to afford the title compound as a white solid (1.31 g, 100%): mp 78-79° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.65 (s, 1H), 7.36 (s, 1H), 3.94 (s, 3H), 3.93 (s, 3H); EIMS m/z 280 ([M]⁺).

Step 2. 2-Chloro-5-methoxy-4-vinylbenzoic acid

A 25 mL round bottomed flask was charged with methyl 4-bromo-2-chloro-5-methoxybenzoate (640 mg, 2.29 mmol), K₂CO₃ (665 mg, 4.81 mmol), potassium trifluoro(vinyl)borate (920 mg, 6.87 mmol), PdCl₂(dppf) (84 mg, 0.11 mmol) and anhydrous DMSO (15 mL) and stirred at 80° C. for 2 h. The reaction was allowed to cool, water (150 mL) was added and then extracted several times with Et₂O. The organic layer was washed with brine, dried over MgSO₄, filtered and concentrated to give a brown residue. The crude product was purified via flash chromatography eluting with 15% Et₂O/hexanes to give methyl 2-chloro-5-methoxy-4-vinylbenzoate as a yellow oil (440 mg, 85%). To a 25 mL round bottomed flask containing methyl 2-chloro-5-methoxy-4-vinylbenzoate (440 mg, 1.94 mmol) and MeOH (10 mL) was added 1N NaOH (2 mL, 2.04 mmol) and reaction stirred at ambient temperature for 18 h. The reaction mixture was concentrated to give a solid residue. The residue was dissolved in water and extracted 1× with 50% Et₂O/hexanes. The aqueous layer was made acidic with 2N HCl and extracted 2× with CH₂Cl₂, dried over MgSO₄, filtered and concentrated to afford the title compound as a white solid (0.39 g, 94%): ¹H NMR (400 MHz, CDCl₃) δ 7.54 (d, J=0.5 Hz, 1H), 7.52 (s, 1H), 6.98 (ddd, J=17.7, 11.2, 0.6 Hz, 1H), 5.87 (dd, J=17.7, 1.1 Hz, 1H), 5.45 (dd, J=11.2, 1.1 Hz, 1H), 3.90 (s, 3H).

Step 3. (E)-2-Chloro-5-methoxy-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid

A 50 mL 3 neck round bottomed flask was charged with 2-chloro-5-methoxy-4-vinylbenzoic acid (390 mg, 1.84 mmol)), 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (754 mg, 2.20 mmol) and anhydrous N-methylpyrrolidinone (10 mL). Nitrogen was bubbled into the reaction mixture for 15 min. After which time, 2,2′-dipyridyl (57.3 mg, 0.37 mmol) and CuBr (11.7 mg, 0.18 mmol) were added and reaction mixture stirred at 150° C. for 1 h. Reaction mixture was allowed to cool, water (300 mL) was added and extracted several times with Et₂O. Organic layer was washed repeatedly with water, dried over MgSO₄, filtered and concentrated to afford—the title compound as a light brown foam (870 mg, 100%). This material was 95% pure by LC/MS; ESIMS m/z 473 ([M−H]⁻). This material was used without further purification.

Step 4. (E)-2-Chloro-5-methoxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

A 50 mL round bottomed flask was charged with (E)-2-chloro-5-methoxy-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (780 mg, 1.65 mmol)), di(1H-imidazol-1-yl)methanone (267 mg, 1.65 mmol) and anhydrous THF (30 mL). The resulting mixture was heated at reflux until it ceased giving off gas. 2-Amino-N-(2,2,2-trifluoroethyl)acetamide HCl (257 mg, 1.65 mmol) was added in one portion and the reaction mixture continued to stir at reflux for 18 h. The reaction mixture was concentrated to dryness and the residue was taken up in Et₂O (50 mL) and 0.1N HCl (10 mL). The layers were separated. The aqueous layer was extracted 2× with Et₂O. The Et₂O layers were combined and washed 1× with aqueous NaHCO₃, 1× with brine, dried over MgSO₄, filtered and concentrated to give a brown oil. The crude product was purified via flash chromatography eluting with 30-40% EtOAc/hexanes to afford the title compound—as an off white foam (280 mg, 28%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 1H), 7.41 (s, 2H), 7.29 (s, 1H), 7.28 (s, 1H), 6.84 (m, 2H), 6.43 (dd, J=16.0, 8.3 Hz, 1H), 4.25 (d, J=5.4 Hz, 2H), 4.10 (m, 1H), 3.97 (qd, J=9.0, 6.4 Hz, 2H), 3.87 (s, 3H); ESIMS m/z 613.1 ([M+H]⁺).

Step 5. (E)-2-Chloro-5-hydroxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

A 25 mL round bottomed flask was charged with (E)-2-chloro-5-methoxy-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (57 mg, 0.093 mmol) and CH₂Cl₂ (3 mL). The reaction mixture was cooled to −78° C. and boron tribromide (BBr₃, 1.0M solution in CH₂Cl₂, 0.33 mL, 0.326 mmol) was added slowly via syringe. The reaction allowed to warm to ambient temperature and stirred for 18 h. An additional 0.3-0.4 mL of BBr₃ was added at ambient temperature and continued to stir for 3 h. The reaction mixture was added to aqueous NaHCO₃ and extracted 3× with CH₂Cl₂. The CH₂Cl₂ layers were combined and dried over MgSO₄, filtered and concentrated to give an oil. The crude material was purified via flash chromatography eluting with 50% EtOAc/hexanes to afford the title compound as a white solid (18 mg, 33%): mp 190° C. (dec.); ¹H NMR (400 MHz, CDCl₃) δ 9.81 (s, 1H), 8.06 (d, J=7.0 Hz, 1H), 7.71 (m, 1H), 7.44 (d, J=2.8 Hz, 2H), 7.37 (s, 1H), 7.20 (s, 1H), 6.82 (d, J=15.9 Hz, 1H), 6.50 (m, 1H), 4.14 (m, 3H), 3.89 (m, 2H); ESIMS m/z 599 ([M+H]⁺).

Example 139 Preparation of 1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-one

To a magnetically stirred solution of 4-bromo-1,2-dichlorobenzene (5.64 g, 24.98 mmol) in dry Et₂O (109 mL) was added n-BuLi (10.86 mL, 24.98 mmol) via an addition funnel under a nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 30 min., A solution of ethyl 2,2-difluoropropanoate (3.0 g, 21.7 mmol) in Et₂O (10 mL) was added dropwise over 15 min and allowed to stir for 1 h. The reaction was then carefully quenched with 1 N HCl (4 mL) and allowed to warm to 23° C. The solution was dilute with Et₂O and washed with water. The combined organic layers were dried over Na₂SO₄, concentrated under reduced pressure and the resulting material was purified via flash column chromatography using 100% hexanes to 5% acetone/95% hexanes as eluent. The relevant fractions were concentrated under reduced pressure to afford the title compound as a colorless oil (3.89 g, 71%): ¹H NMR (400 MHz, CDCl₃) δ 8.21-8.18 (m, 1H), 7.99-7.93 (m, 1H), 7.59 (dd, J=8.4, 4.2 Hz, 1H), 1.89 (t, J=19.6 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −92.08-−93.21 (m); EISMS m/z 240 ([M−H]⁺).

Example 140 (E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-vinylbenzoic acid

To a stirred solution of (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (600 mg, 1.23 mmol) in dry toluene (10 mL) was added tributyl(vinyl)stannane (470 mg, 1.48 mmol) and the mixture was degassed with argon for 15 min Pd(PPh₃)₄ (72 mg, 0.06 mmol) was added and the reaction mixture was refluxed for 2 h. The reaction mixture was brought to ambient temperature, water was added and the mixture extracted with EtOAc. The organic layer was washed with 2N HCl and brine, dried (Na₂SO₄), filtered, and concentrated. The residue was purified by column chromatography on silica eluting with 30% EtOAc in petroleum ether to afford the title compound as brown solid (295 mg, 55%): ¹H NMR (300 MHz, DMSO-d₆) δ 13.05 (bs, 1H), 7.91 (s, 2H), 7.81-7.75 (m, 2H), 7.59 (d, J=8.1 Hz, 1H), 7.48 (dd, J=17.4, 10.8 Hz, 1H), 7.03 (dd, J=15.9, 8.7 Hz, 1H), 6.84 (d, J=15.6 Hz, 1H), 5.88 (d, J=16.5 Hz, 1H), 5.39 (d, J=12.3 Hz, 1H), 4.89-4.82 (m, 1H); ESIMS m/z 432.18 ([M−H]⁻); IR (thinfilm) 3418, 1689, 1114, 747 cm⁻¹.

Example 141 (E)-2-Iodo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid

Per Buchwald, et al.; JACS, 2002, 124, 14844-14845, potassium iodide (KI, 273 mg, 1.64 mmol), CuI (31 mg, 0.16 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (catalytic amount) were added to a solution of (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (400 mg, 0.82 mmol) in 1,4-dioxane (8 mL). The mixture in an Ace pressure tube was heated at 100° C. for 3 h. The reaction mixture was brought to ambient temperature and filtered through a Celite® pad. The filtrate was concentrated and residue was diluted with EtOAc and washed with 1N HCl followed by brine. The organic layer was dried (Na₂SO₄), filtered, and concentrated. The residue was purified by column chromatography on silica eluting with 25% EtOAc in petroleum ether to afford the title compound as brown semi solid (240 mg, 55%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.3 (bs, 1H), 8.21 (s, 1H), 7.91 (s, 2H), 7.71-7.64 (m, 2H), 7.01 (dd, J=15.6, 9.2 Hz, 1H), 6.75 (d, J=15.6 Hz, 1H), 4.85-4.81 (m, 1H); ESIMS m/z 532.8 ([M−H]⁻); IR (thinfilm) 3436, 1699, 1113, 750 cm⁻¹.

Example 142 Preparation of (E)-2-Bromo-N-(2-methyl-1-(neopentylamino)-1-oxopropan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

Step 1. (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)-2-methylpropanoic acid

A 25 mL round bottomed flask equipped with a magnetic stir bar and reflux condenser was charged with (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (400 mg, 0.82 mmol) and 1,2-dichloroethane (DCE) (5 mL). Thionyl chloride (0.12 mL, 1.64 mmol) was added neat in one portion and the resulting reaction mixture was heated at reflux for 2 h. After which time, reaction mixture was allowed to cool and concentrated to give the crude acid chloride which was used without further purification. To a solution containing NaHCO₃ (68.8 mg, 0.82 mmol), 2-amino-2-methylpropanoic acid (84 mg, 0.82 mmol) and dodecyltrimethylammonium bromide (2.52 mg, 8.19 μmol) in 10 mL of THF was added to the acid chloride in THF (1 mL). The resulting mixture was heated at reflux for 18 h. Reaction mixture was allowed to cool and added to water, made acidic with 0.1N HCl, extracted (3×) with Et₂O, washed (1×) with brine, dried over MgSO₄, filtered and evaporated to afford the title compound as a light brown foam (400 mg, 85%): ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J=1.6 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.37 (dd, J=8.1, 1.6 Hz, 1H), 6.63 (s, 1H), 6.53 (d, J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.10 (p, J=8.3 Hz, 1H), 1.73 (s, 6H). This material is used without further purification.

Step 2. (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-4,4-dimethyloxazol-5(4H)-one

A 25 mL round bottomed flask was charged with (E)-2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)-2-methylpropanoic acid (400 mg, 0.70 mmol), CH₂Cl₂ (10 mL) and stirred at 0° C. EDC.HCl (134 mg, 0.70 mmol) was added in one portion as a solid and the reaction mixture was allowed to warm toward ambient temperature and continued to stir for 1 h. The reaction was diluted with CH₂Cl₂, washed with brine, dried over MgSO₄, filtered and evaporated to give a dark oil. The crude product was purified via flash chromatography eluting with 50% hexanes/CH₂Cl₂ to afford the title compound as an off white foam (220 mg, 57): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.1 Hz, 1H), 7.73 (d, J=1.6 Hz, 1H), 7.42 (d, J=7.8 Hz, 3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.7 Hz, 1H), 4.12 (p, J=8.5 Hz, 1H), 1.57 (s, 6H); ¹⁹F NMR (376 MHz, CDCl₃) δ −68.55; ESIMS m/z 554 ([M−H]⁻).

Step 3. (E)-2-Bromo-N-(2-methyl-1-(neopentylamino)-1-oxopropan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

A 10 mL round bottomed flask was charged with (E)-2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-4,4-dimethyloxazol-5(4H)-one (90 mg, 0.16 mmol) and CH₂Cl₂ (2 mL). 2,2-Dimethylpropan-1-amine (28.2 mg, 0.324 mmol) was added neat via pipette and the reaction stirred at ambient temperature for 18 h. The reaction mixture was evaporated to give an oil. The crude product was purified via flash chromatography eluting with 20% EtOAc/hexanes to afford the title compound as a white foam (90 mg, 86%): ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J=1.6 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.36 (dd, J=8.1, 1.6 Hz, 1H), 6.66 (d, J=10.0 Hz, 2H), 6.53 (d, J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.8 Hz, 1H), 4.11 (m, 1H), 3.12 (d, J=6.2 Hz, 2H), 1.72 (s, 6H), 0.93 (s, 9H); ¹⁹F NMR (376 MHz, CDCl₃) δ −68.62; ESIMS m/z 643.19 ([M+H]⁺).

Example 143 Preparation of 3,5-Dibromo-4-chlorobenzaldehyde

Step 1. Methyl 4-amino-3,5-dibromobenzoate: conc.

H₂SO₄ (1.35 mL, 25.48 mmol) was added dropwise to a stirred solution of 4-amino-3,5-dibromobenzoic acid (5.0 g, 16.99 mmol) in MeOH (50 mL) at ambient temperature and the reaction mixture was then stirred at 80° C. for 8 h. The reaction mixture was brought to ambient temperature, volatiles were evaporated and ice cold water was added to the residue and which was then extracted with EtOAc. The organic layer was washed with an aqueous NaHCO₃ solution followed by brine and water. The solution was then dried (Na₂SO₄), filtered and concentrated to afford the title compound as an off white solid (5.0 g, 95%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.91 (s, 2H), 6.20 (bs, 2H), 3.78 (s, 3H); ESIMS m/z 307.0 ([M]⁺); IR (thin film) 3312, 2953, 1726, 595 cm⁻¹.

Step 2. Methyl 3,5-dibromo-4-chlorobenzoate

CuCl₂ (2.82 g, 21.0 mmol) in MeCN (30 mL) was stirred at 80° C. for 30 min. To this mixture tert-butylnitrite (2.7 mL, 23 mmol) was then added dropwise at same temperature and the mixture was stirred for another 10 min. Methyl 4-amino-3,5-dibromobenzoate (5.0 g, 16 mmol) in MeCN (30 mL) was added dropwise to the reaction mixture and then stirred at 80° C. for 30 min. The reaction mixture was brought to ambient temperature and an aqueous ammonia solution (20 mL) was added to the reaction mixture and extracted with petroleum ether. The organic layer was washed with brine followed by water, dried (Na₂SO₄), filtered and concentrated to afford the title compound as an off white solid (4.5 g, 84%). ¹H NMR (300 MHz, DMSO-d₆) δ 8.21 (s, 2H), 3.94 (s, 3H); ESIMS m/z 326 ([M]⁺); IR (thin film) 1732, 746 cm⁻¹.

Step 3. (3,5-Dibromo-4-chlorophenyl)methanol

NaBH₄ (1.53 g, 40.65 mmol) was added portionwise to a stirred solution of methyl 3,5-dibromo-4-chlorobenzoate (4.45 g, 13.6 mmol) in MeOH (50 mL) at 0° C. The reaction mixture was then stirred at ambient temperature for 8 h. The volatiles were evaporated and the residue was diluted with CH₂Cl₂ and washed with brine followed by water. The organic layer was dried (Na₂SO₄), filtered and concentrated to afford the title compound as an off white solid (3.3 g, 80%): ¹H NMR (300 MHz, DMSO-d₆) δ 7.71 (s, 2H), 5.49 (bs, 1H), 4.48 (d, J=4.5 Hz, 2H); ESIMS m/z 297.9 ([M]⁺); IR (thin film) 3460, 747, 534 cm⁻¹.

Step 4. 3,5-Dibromo-4-chlorobenzaldehyde

Pyridinium chlorochormate (PCC, 3.44 g, 15.9 mmol) was added in one portion to a stirred solution of (3,5-dibromo-4-chlorophenyl)methanol (3.2 g, 11.0 mmol) in CHCl₃ (40 mL) at ambient temperature and the reaction mixture was stirred overnight. The reaction mixture was filtered through Celite®, the Celite® pad was washed with CHCl₃ and the filtrate was concentrated to afford the title compound as an off white solid (2.0 g, 62%): mp 110-113° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.93 (s, 1H), 8.27 (s, 2H); ESIMS m/z 297.0 ([M]⁺).

Example 144 Preparation of 4-Bromo-3,5-dichlorobenzaldehyde

Step 1. Methyl 4-amino-3,5-dichlorobenzoate: conc.

H₂SO₄ (2.5 mL, 97.04 mmol) was added drop wise to a stirred solution of 4-amino-3,5-dichlorobenzoic acid (10.0 g, 48.54 mmol) in MeOH (150 mL) at 0° C. and the reaction mixture was then stirred at 80° C. for 8 h. The volatiles were evaporated; ice cold water was added to the residue and which was then extracted with EtOAc. The combined organic layers were washed with brine, dried (Na₂SO₄), filtered and concentrated under reduced pressure to afford the title compound as a white solid (7.5 g, 70%): ¹H NMR (300 MHz, DMSO-d₆) δ 8.05 (s, 2H), 3.96 (s, 3H); ESIMS m/z 282 ([M]⁺); IR (KBr): 1733, 762, 514 cm⁻¹.

Step 2. Methyl 4-bromo-3,5-dichlorobenzoate

CuBr₂ (7.5 g, 34.08 mmol) in MeCN (50 mL) was stirred at 80° C. for 30 min. To this solution tert-butylnitrite (6.5 mL, 54.55 mmol) was added dropwise at the same temperature and the mixture was stirred for another 10 min. Methyl 4-amino-3,5-dichlorobenzoate in MeCN (30 mL) was added dropwise to the reaction mixture which was then stirred at 80° C. for 30 min. The reaction mixture was brought to ambient temperature. Aqueous ammonia solution (20 mL) was added and extracted with petroleum ether. The organic layer was washed with brine followed by water. The organic solution was dried (Na₂SO₄), filtered and concentrated to afford the title compound as an off white solid (7.5 g, 77%): ¹H NMR (300 MHz, DMSO-d₆) δ 8.02 (s, 2H), 3.94 (s, 3H); ESIMS m/z 282 ([M]⁺); IR (thin film) 1733, 762, 514 cm⁻¹.

Step 3. (4-Bromo-3,5-dichlorophenyl)methanol

DIBAL-H (1M in toluene, 66 mL, and 66.0 mmol) was added dropwise to a stirred solution of methyl 4-bromo-3,5-dichlorobenzoate (7.5 g, 26.0 mmol) in THF (50 mL) at −78° C. The reaction mixture was brought to ambient temperature and stirred for 6 h. The reaction mixture was poured into ice-water and extracted with CH₂Cl₂. The organic layer was washed with brine followed by water, dried (Na₂SO₄), filtered and concentrated to afford a mixture of (4-bromo-3,5-dichlorophenyl)methanol and 4-bromo-3,5-dichlorobenzaldehyde (6.0 g) as an off white solid which was taken to next step without purification.

Step 4. 4-Bromo-3,5-dichlorobenzaldehyde

PCC (7.5 g, 35.16 mmol) was added in one portion to a stirred solution containing a mixture of (4-bromo-3,5-dichlorophenyl)methanol and 4-bromo-3,5-dichlorobenzaldehyde (6.0 g) in CHCl₃ (40 mL) at ambient temperature and the reaction mixture was stirred overnight. The reaction mixture was filtered through celite. The celite pad was washed with CHCl₃. The filtrate was concentrated to afford the title compound as an off white solid (3.5 g, 67%): mp 125-128° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 9.96 (s, 1H), 8.10 (s, 2H); ESIMS m/z 252 ([M]⁺).

Example 145 3-Chloro-5-ethylbenzaldehyde

PdCl₂(dppf)(37 mg, 0.046 mmol), potassium phosphate (1.93 g, 9.11 mmol) and triethylborane (1M in hexane, 0.45 g, 4.56 mmol) were added to a solution of 3-bromo-5-chloro-benzaldehyde (1.0 g, 4.56 mmol) in THF (20 mL) at ambient temperature and the mixture was refluxed for 12 h. The reaction mixture was brought to ambient temperature, diluted with EtOAc and washed with water. The organic layer was dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 2% EtOAc in petroleum ether to afford the title compound (330 mg, 41%) as a pale yellow liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 9.97 (s, 1H), 7.75 (d, J=1.6 Hz 1H), 7.73 (s, 1H), 7.65 (s, 1H), 2.74-2.68 (m, 2H), 1.23 (t, J=7.6 Hz, 3H); ESIMS m/z 168.0 ([M]⁺); IR (thin film) 3071, 1699, 692 cm⁻¹.

Example 146 (E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

Step 1. (E)-Ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoate

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.5 g, 10.8 mmol), CuCl (54 mg, 0.54 mmol) and 2,2-bipyridyl (169 mg, 1.08 mmol) were added to a stirred solution of ethyl 2-nitro-4-vinylbenzoate (1.2 g, 5.42 mmol) in 1,2-dichlorobenzene (12 mL) at ambient temperature and the mixture was then stirred at 180° C. for 18 h. The reaction mixture was then cooled to ambient temperature, adsorbed on silica gel and purified by column chromatography eluting with 10% EtOAc in petroleum ether to afford the title compound (1.3 g, 53%) as a brown liquid: ¹H NMR (DMSO-d₆, 300 MHz) δ 8.31 (s, 1H), 8.02-7.95 (m, 1H), 7.88-7.85 (m, 3H), 7.20 (dd, J=15.9, 9.3 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.91-4.85 (m, 1H), 4.34-4.27 (m, 2H), 1.27 (t, J=6.6 Hz, 3H); ESIMS m/z 463.8 ([M−H]⁻); IR (KBr) 3439, 2985, 1731, 1251 cm⁻¹.

Step 2. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoic acid

Concentrated HCl (16.0 mL) was added dropwise to a stirred solution of (E)-ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoate (800 mg, 1.72 mmol) in 1,4-dioxane (8.0 mL) at 0° C. and the reaction mixture was refluxed for 36 h. The volatiles were evaporated; the residue was diluted with EtOAc and washed with brine and water. The organic layer was dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 30% EtOAc in petroleum ether to afford the title compound as a yellow solid (390 mg, 52%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.9 (bs, 1H), 8.22 (s, 1H), 7.93-7.91 (m, 1H), 7.86-7.84 (m, 3H), 7.16 (dd, J=15.6, 9.2 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H), 4.89-4.85 (m, 1H). ESIMS m/z 435.9 ([M−H]⁻); IR (KBr) 3445, 2924, 1708, 1541, 817 cm⁻¹.

Step 3. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitro-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

2-Amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (96 mg, 0.35 mmol), PyBOP (165 mg, 0.32 mmol) and DIPEA (0.1 mL, 0.57 mmol) were added to a stirred solution of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoic acid (130 mg, 0.29 mmol) in CH₂Cl₂ (3 mL) and the reaction mixture was stirred at ambient temperature for 8 h. Water was added to reaction mixture and extracted with CH₂Cl₂. The organic layer was washed with brine, dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 30% EtOAc in petroleum ether to afford the title compound as a yellow solid (120 mg, 74%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.04 (t, J=5.7 Hz, 1H), 8.60 (t, J=6.0 Hz, 1H), 8.25 (s, 1H), 7.97-7.94 (m, 1H), 7.87 (d, J=6.3 Hz, 2H), 7.69 (d, J=7.5 Hz, 1H), 7.15 (dd, J=15.9, 9.3 Hz, 1H), 6.89 (d, J=15.9 Hz, 1H), 4.88-4.83 (m, 1H), 3.98-3.89 (m, 4H); ESIMS m/z 575.87 ([M+H]⁺); IR (KBr) 3430, 2925, 1663, 1168, 832 cm⁻¹.

Step 4. (E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

Iron powder (81.8 mg, 1.46 mmol) and NH₄Cl (104 mg, 1.94 mmol) was added to a stirred solution of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitro-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide (280 mg, 0.486 mmol) in EtOH:water (6 mL, 1:1) at ambient temperature and the mixture was stirred at reflux for 90 min. The reaction mixture was cooled to ambient temperature and filtered through celite. The filtrate was concentrated and the residue was dissolved in EtOAc and washed with saturated NaHCO₃ solution, brine and water. The organic layer was dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (10-200 mesh) eluting with 35% EtOAc in petroleum ether to afford the titled compound as a yellow solid (215 mg, 81%).

Example 147 (E)-2-Bromo-4-(3-(3,5-dichloro-4-hydroxyphenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

DIPEA (0.20 mL, 1.26 mmol), PyBOP (245 mg, 0.47 mmol) and 2-amino-N-(2,2,2-trifluoroethyl)acetamide (90 mg, 0.47 mmol) were added to a stirred solution of (E)-2-bromo-4-(3-(3,5-dichloro-4-hydroxyphenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (200 mg, 0.42 mmol, 66% purity) in CH₂Cl₂ (5 mL) at ambient temperature. The resulting mixture was then stirred for 12 h. The reaction mixture was diluted with CH₂Cl₂, washed with 1N HCl, followed by saturated sodium bicarbonate solution, brine solution and water. The organic layer was dried (Na₂SO₄), filtered, concentrated under vacuum. The residue was purified by column chromatography on silica (100-200 mesh) eluting with 30% EtOAc in petroleum ether to give the title compound as light green solid (130 mg, 52%).

Example 148 Preparation of (R)-2-Amino-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

A Parr shaker flask charged with (R)-benzyl (3-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)-butan-2-yl)carbamate (4.95 g, 14.9 mmol) in 100 mL of EtOAc and 25 mL of EtOH was treated with 175 mg of 10% Pd/C. The mixture was placed under 40 psi of hydrogen and shaken for 6 h. An additional 65 mg of 10% Pd/C was added to the reaction mixture which was then placed under 40 psi of hydrogen and shaken for 3.5 h. The reaction solution was then filtered through a pad of celite, concentrated in vacuo and purified by sublimation (75 to 85° C., 200-230 millibar) to afford the title compound as a white solid (1.92 g, 65%): mp 43-47° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.04-7.74 (m, 1H), 3.92 (ddd, J=16.0, 9.3, 6.8 Hz, 1H), 3.84-3.60 (m, 1H), 3.23 (d, J=3.8 Hz, 1H), 2.23 (ddd, J=10.7, 7.0, 3.5 Hz, 1H), 0.92 (d, J=7.0 Hz, 3H), 0.75 (d, J=6.9 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −72.70.

Example 149 Preparation of (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(methylsulfonyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

Oxone (320 mg, 0.50 mmol) was added to a stirred solution of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(methylthio)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide (150 mg, 0.25 mmol) in acetone-water (10 mL, 1:1) at ambient temperature and the reaction mixture was stirred for 18 h. The reaction mixture was then extracted with CH₂Cl₂. The organic layer was washed with brine and water, dried (Na₂SO₄), filtered, concentrated and the residue was triturated with pentane-Et₂O (1:1) to afford the title compound as an off white solid (85 mg, 56%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.01 (t, J=6.0, 1H), 8.37 (t, J=6.4 Hz, 1H), 8.08 (s, 1H), 8.01-7.96 (m, 1H), 7.88-7.86 (m, 2H), 7.64 (d, J=7.6 Hz, 1H), 7.05 (dd, J=16.4, 8.8 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.87-4.80 (m, 1H), 3.98-3.91 (m, 4H), 3.38 (s, 3H); ESIMS m/z 608.85 ([M+H]⁺); IR (thin film) 337, 416, 721, 164, 768 cm⁻¹.

The following prophetic molecules could be made in accordance with the procedures disclosed in this application:

Compound Number Structure P1

P2

P3

P4

P5

P6

P7

P8

P9

P10

P11

P12

P13

P14

P15

P16

P17

P18

P19

P20

P21

P22

P23

P24

P25

P26

P27

P28

P29

P30

P31

P32

P33

P34

P35

P36

P37

P38

P39

P40

P41

P42

P43

P44

P45

The following prophetic molecules could be made in accordance with the procedures disclosed in this application:

Cmpd No. R1 R2 R3 R4 R6 R8 R10 W1 (C1-C8) alkyl W2 R15 P46 F F F H CF₃ H Br O CH₂ O CH₂CF₃ P47 F F F H CF₃ H Cl O CH₂ O CH₂CF₃ P48 F F F H CF₃ H CF₃ O CH₂ O CH₂CF₃ P49 F F F H CF₃ H CH₃ O CH₂ O CH₂CF₃ P50 F F F H CF₃ H Br O CH₂ S CH₂CF₃ P51 F F F H CF₃ H Cl O CH₂ S CH₂CF₃ P52 F F F H CF₃ H CF₃ O CH₂ S CH₂CF₃ P53 F F F H CF₃ H CH₃ O CH₂ S CH₂CF₃ P54 F F F H CF₃ H Br S CH₂ O CH₂CF₃ P55 F F F H CF₃ H Cl S CH₂ O CH₂CF₃ P56 F F F H CF₃ H CF₃ S CH₂ O CH₂CF₃ P57 F F F H CF₃ H CH₃ S CH₂ O CH₂CF₃ P58 F F F H CF₃ H Br O CH₂ O CH₂CHF₂ P59 F F F H CF₃ H Cl O CH₂ O CH₂CHF₂ P60 F F F H CF₃ H CF₃ O CH₂ O CH₂CHF₂ P61 F F F H CF₃ H CH₃ O CH₂ O CH₂CHF₂ P62 F F F H CF₃ CF₃ Br O CH₂ O CH₂CF₃ P63 F F F H CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P64 F F F H CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P65 F F F H CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P66 F F F H CF₂CF₃ H Br O CH₂ O CH₂CF₃ P67 F F F H CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P68 F F F H CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P69 F F F H CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P70 F F F H CF₃ H Br O CH₂ O CH(CH₃)CF₃ P71 F F F H CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P72 F F F H CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P73 F F F H CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P74 F F F H CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P75 F F F H CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P76 F F F H CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P77 F F F H CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P78 F F F H CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P79 F F F H CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P80 F F F H CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P81 F F F H CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P82 F F F H CF₃ H Br O CH(CH₃) O CH₂CF₃ P83 F F F H CF₃ H Cl O CH (CH₃) O CH₂CF₃ P84 F F F H CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P85 F F F H CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P86 F F F H CF₃ H Br O CH(CH₃) S CH₂CF₃ P87 F F F H CF₃ H Cl O CH (CH₃) S CH₂CF₃ P88 F F F H CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P89 F F F H CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P90 F F F H CF₃ H Br S CH(CH₃) O CH₂CF₃ P91 F F F H CF₃ H Cl S CH (CH₃) O CH₂CF₃ P92 F F F H CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P93 F F F H CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P94 F F F H CF₃ H Br O CH(CH₃) O CH₂CHF₂ P95 F F F H CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P96 F F F H CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P97 F F F H CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P98 F F F H CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P99 F F F H CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P100 F F F H CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P101 F F F H CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P102 F F F H CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P103 F F F H CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P104 F F F H CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P105 F F F H CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P106 F F F H CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P107 F F F H CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P108 F F F H CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P109 F F F H CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P110 F F F H CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P111 F F F H CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P112 F F F H CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P113 F F F H CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P114 F F F H CF₃ H Br O CH₂CH₂ O CH₂CF₃ P115 F F F H CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P116 F F F H CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P117 F F F H CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P118 Cl Cl H Cl CF₃ H Br O CH₂ O CH₂CF₃ P119 Cl Cl H Cl CF₃ H Cl O CH₂ O CH₂CF₃ P120 Cl Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P121 Cl Cl H Cl CF₃ H CH₃ O CH₂ O CH₂CF₃ P122 Cl Cl H Cl CF₃ H Br O CH₂ S CH₂CF₃ P123 Cl Cl H Cl CF₃ H Cl O CH₂ S CH₂CF₃ P124 Cl Cl H Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P125 Cl Cl H Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P126 Cl Cl H Cl CF₃ H Br S CH₂ O CH₂CF₃ P127 Cl Cl H Cl CF₃ H Cl S CH₂ O CH₂CF₃ P128 Cl Cl H Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P129 Cl Cl H Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P130 Cl Cl H Cl CF₃ H Br O CH₂ O CH₂CHF₂ P131 Cl Cl H Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P132 Cl Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P133 Cl Cl H Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P134 Cl Cl H Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P135 Cl Cl H Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P136 Cl Cl H Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P137 Cl Cl H Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P138 Cl Cl H Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P139 Cl Cl H Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P140 Cl Cl H Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P141 Cl Cl H Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P142 Cl Cl H Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P143 Cl Cl H Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P144 Cl Cl H Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P145 Cl Cl H Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P146 Cl Cl H Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P147 Cl Cl H Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P148 Cl Cl H Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P149 Cl Cl H Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P150 Cl Cl H Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P151 Cl Cl H Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P152 Cl Cl H Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P153 Cl Cl H Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P154 Cl Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P155 Cl Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P156 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P157 Cl Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P158 Cl Cl H Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P159 Cl Cl H Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P160 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P161 Cl Cl H Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P162 Cl Cl H Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P163 Cl Cl H Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P164 Cl Cl H Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P165 Cl Cl H Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P166 Cl Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P167 Cl Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P168 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P169 Cl Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P170 Cl Cl H Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P171 Cl Cl H Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P172 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P173 Cl Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P174 Cl Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P175 Cl Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P176 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P177 Cl Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P178 Cl Cl H Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P179 Cl Cl H Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P180 Cl Cl H Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P181 Cl Cl H Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P182 Cl Cl H Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P183 Cl Cl H Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P184 Cl Cl H Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P185 Cl Cl H Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P186 Cl Cl H Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P187 Cl Cl H Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P188 Cl Cl H Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P189 Cl Cl H Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P190 H H H OCF₃ CF₃ H Br O CH₂ O CH₂CF₃ P191 H H H OCF₃ CF₃ H Cl O CH₂ O CH₂CF₃ P192 H H H OCF₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P193 H H H OCF₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P194 H H H OCF₃ CF₃ H Br O CH₂ S CH₂CF₃ P195 H H H OCF₃ CF₃ H Cl O CH₂ S CH₂CF₃ P196 H H H OCF₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P197 H H H OCF₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P198 H H H OCF₃ CF₃ H Br S CH₂ O CH₂CF₃ P199 H H H OCF₃ CF₃ H Cl S CH₂ O CH₂CF₃ P200 H H H OCF₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P201 H H H OCF₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P202 H H H OCF₃ CF₃ H Br O CH₂ O CH₂CHF₂ P203 H H H OCF₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P204 H H H OCF₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P205 H H H OCF₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P206 H H H OCF₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P207 H H H OCF₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P208 H H H OCF₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P209 H H H OCF₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P210 H H H OCF₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P211 H H H OCF₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P212 H H H OCF₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P213 H H H OCF₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P214 H H H OCF₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P215 H H H OCF₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P216 H H H OCF₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P217 H H H OCF₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P218 H H H OCF₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P219 H H H OCF₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P220 H H H OCF₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P221 H H H OCF₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P222 H H H OCF₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P223 H H H OCF₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P224 H H H OCF₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P225 H H H OCF₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P226 H H H OCF₃ CF₃ H Br O CH(CH₃) O CH₂CF₃ P227 H H H OCF₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P228 H H H OCF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P229 H H H OCF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P230 H H H OCF₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P231 H H H OCF₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P232 H H H OCF₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P233 H H H OCF₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P234 H H H OCF₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P235 H H H OCF₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P236 H H H OCF₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P237 H H H OCF₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P238 H H H OCF₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P239 H H H OCF₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P240 H H H OCF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P241 H H H OCF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P242 H H H OCF₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P243 H H H OCF₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P244 H H H OCF₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P245 H H H OCF₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P246 H H H OCF₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P247 H H H OCF₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P248 H H H OCF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P249 H H H OCF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P250 H H H OCF₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P251 H H H OCF₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P252 H H H OCF₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P253 H H H OCF₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P254 H H H OCF₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P255 H H H OCF₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P256 H H H OCF₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P257 H H H OCF₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P258 H H H OCF₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P259 H H H OCF₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P260 H H H OCF₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P261 H H H OCF₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P262 H F H Br CF₃ H Br O CH₂ O CH₂CF₃ P263 H F H Br CF₃ H Cl O CH₂ O CH₂CF₃ P264 H F H Br CF₃ H CF₃ O CH₂ O CH₂CF₃ P265 H F H Br CF₃ H CH₃ O CH₂ O CH₂CF₃ P266 H F H Br CF₃ H Br O CH₂ S CH₂CF₃ P267 H F H Br CF₃ H Cl O CH₂ S CH₂CF₃ P268 H F H Br CF₃ H CF₃ O CH₂ S CH₂CF₃ P269 H F H Br CF₃ H CH₃ O CH₂ S CH₂CF₃ P270 H F H Br CF₃ H Br S CH₂ O CH₂CF₃ P271 H F H Br CF₃ H Cl S CH₂ O CH₂CF₃ P272 H F H Br CF₃ H CF₃ S CH₂ O CH₂CF₃ P273 H F H Br CF₃ H CH₃ S CH₂ O CH₂CF₃ P274 H F H Br CF₃ H Br O CH₂ O CH₂CHF₂ P275 H F H Br CF₃ H Cl O CH₂ O CH₂CHF₂ P276 H F H Br CF₃ H CF₃ O CH₂ O CH₂CHF₂ P277 H F H Br CF₃ H CH₃ O CH₂ O CH₂CHF₂ P278 H F H Br CF₃ CF₃ Br O CH₂ O CH₂CF₃ P279 H F H Br CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P280 H F H Br CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P281 H F H Br CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P282 H F H Br CF₂CF₃ H Br O CH₂ O CH₂CF₃ P283 H F H Br CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P284 H F H Br CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P285 H F H Br CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P286 H F H Br CF₃ H Br O CH₂ O CH(CH₃)CF₃ P287 H F H Br CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P288 H F H Br CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P289 H F H Br CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P290 H F H Br CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P291 H F H Br CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P292 H F H Br CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P293 H F H Br CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P294 H F H Br CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P295 H F H Br CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P296 H F H Br CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P297 H F H Br CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P298 H F H Br CF₃ H Br O CH(CH₃) O CH₂CF₃ P299 H F H Br CF₃ H Cl O CH (CH₃) O CH₂CF₃ P300 H F H Br CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P301 H F H Br CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P302 H F H Br CF₃ H Br O CH(CH₃) S CH₂CF₃ P303 H F H Br CF₃ H Cl O CH (CH₃) S CH₂CF₃ P304 H F H Br CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P305 H F H Br CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P306 H F H Br CF₃ H Br S CH(CH₃) O CH₂CF₃ P307 H F H Br CF₃ H Cl S CH (CH₃) O CH₂CF₃ P308 H F H Br CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P309 H F H Br CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P310 H F H Br CF₃ H Br O CH(CH₃) O CH₂CHF₂ P311 H F H Br CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P312 H F H Br CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P313 H F H Br CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P314 H F H Br CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P315 H F H Br CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P316 H F H Br CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P317 H F H Br CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P318 H F H Br CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P319 H F H Br CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P320 H F H Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P321 H F H Br CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P322 H F H Br CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P323 H F H Br CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P324 H F H Br CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P325 H F H Br CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P326 H F H Br CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P327 H F H Br CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P328 H F H Br CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P329 H F H Br CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P330 H F H Br CF₃ H Br O CH₂CH₂ O CH₂CF₃ P331 H F H Br CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P332 H F H Br CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P333 H F H Br CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P334 H CH₃ Cl H CF₃ H Br O CH₂ O CH₂CF₃ P335 H CH₃ Cl H CF₃ H Cl O CH₂ O CH₂CF₃ P336 H CH₃ Cl H CF₃ H CF₃ O CH₂ O CH₂CF₃ P337 H CH₃ Cl H CF₃ H CH₃ O CH₂ O CH₂CF₃ P338 H CH₃ Cl H CF₃ H Br O CH₂ S CH₂CF₃ P339 H CH₃ Cl H CF₃ H Cl O CH₂ S CH₂CF₃ P340 H CH₃ Cl H CF₃ H CF₃ O CH₂ S CH₂CF₃ P341 H CH₃ Cl H CF₃ H CH₃ O CH₂ S CH₂CF₃ P342 H CH₃ Cl H CF₃ H Br S CH₂ O CH₂CF₃ P343 H CH₃ Cl H CF₃ H Cl S CH₂ O CH₂CF₃ P344 H CH₃ Cl H CF₃ H CF₃ S CH₂ O CH₂CF₃ P345 H CH₃ Cl H CF₃ H CH₃ S CH₂ O CH₂CF₃ P346 H CH₃ Cl H CF₃ H Br O CH₂ O CH₂CHF₂ P347 H CH₃ Cl H CF₃ H Cl O CH₂ O CH₂CHF₂ P348 H CH₃ Cl H CF₃ H CF₃ O CH₂ O CH₂CHF₂ P349 H CH₃ Cl H CF₃ H CH₃ O CH₂ O CH₂CHF₂ P350 H CH₃ Cl H CF₃ CF₃ Br O CH₂ O CH₂CF₃ P351 H CH₃ Cl H CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P352 H CH₃ Cl H CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P353 H CH₃ Cl H CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P354 H CH₃ Cl H CF₂CF₃ H Br O CH₂ O CH₂CF₃ P355 H CH₃ Cl H CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P356 H CH₃ Cl H CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P357 H CH₃ Cl H CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P358 H CH₃ Cl H CF₃ H Br O CH₂ O CH(CH₃)CF₃ P359 H CH₃ Cl H CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P360 H CH₃ Cl H CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P361 H CH₃ Cl H CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P362 H CH₃ Cl H CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P363 H CH₃ Cl H CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P364 H CH₃ Cl H CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P365 H CH₃ Cl H CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P366 H CH₃ Cl H CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P367 H CH₃ Cl H CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P368 H CH₃ Cl H CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P369 H CH₃ Cl H CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P370 H CH₃ Cl H CF₃ H Br O CH(CH₃) O CH₂CF₃ P371 H CH₃ Cl H CF₃ H Cl O CH (CH₃) O CH₂CF₃ P372 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P373 H CH₃ Cl H CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P374 H CH₃ Cl H CF₃ H Br O CH(CH₃) S CH₂CF₃ P375 H CH₃ Cl H CF₃ H Cl O CH (CH₃) S CH₂CF₃ P376 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P377 H CH₃ Cl H CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P378 H CH₃ Cl H CF₃ H Br S CH(CH₃) O CH₂CF₃ P379 H CH₃ Cl H CF₃ H Cl S CH (CH₃) O CH₂CF₃ P380 H CH₃ Cl H CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P381 H CH₃ Cl H CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P382 H CH₃ Cl H CF₃ H Br O CH(CH₃) O CH₂CHF₂ P383 H CH₃ Cl H CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P384 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P385 H CH₃ Cl H CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P386 H CH₃ Cl H CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P387 H CH₃ Cl H CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P388 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P389 H CH₃ Cl H CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P390 H CH₃ Cl H CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P391 H CH₃ Cl H CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P392 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P393 H CH₃ Cl H CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P394 H CH₃ Cl H CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P395 H CH₃ Cl H CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P396 H CH₃ Cl H CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P397 H CH₃ Cl H CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P398 H CH₃ Cl H CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P399 H CH₃ Cl H CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P400 H CH₃ Cl H CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P401 H CH₃ Cl H CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P402 H CH₃ Cl H CF₃ H Br O CH₂CH₂ O CH₂CF₃ P403 H CH₃ Cl H CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P404 H CH₃ Cl H CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P405 H CH₃ Cl H CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P406 H Cl CH₃ H CF₃ H Br O CH₂ O CH₂CF₃ P407 H Cl CH₃ H CF₃ H Cl O CH₂ O CH₂CF₃ P408 H Cl CH₃ H CF₃ H CF₃ O CH₂ O CH₂CF₃ P409 H Cl CH₃ H CF₃ H CH₃ O CH₂ O CH₂CF₃ P410 H Cl CH₃ H CF₃ H Br O CH₂ S CH₂CF₃ P411 H Cl CH₃ H CF₃ H Cl O CH₂ S CH₂CF₃ P412 H Cl CH₃ H CF₃ H CF₃ O CH₂ S CH₂CF₃ P413 H Cl CH₃ H CF₃ H CH₃ O CH₂ S CH₂CF₃ P414 H Cl CH₃ H CF₃ H Br S CH₂ O CH₂CF₃ P415 H Cl CH₃ H CF₃ H Cl S CH₂ O CH₂CF₃ P416 H Cl CH₃ H CF₃ H CF₃ S CH₂ O CH₂CF₃ P417 H Cl CH₃ H CF₃ H CH₃ S CH₂ O CH₂CF₃ P418 H Cl CH₃ H CF₃ H Br O CH₂ O CH₂CHF₂ P419 H Cl CH₃ H CF₃ H Cl O CH₂ O CH₂CHF₂ P420 H Cl CH₃ H CF₃ H CF₃ O CH₂ O CH₂CHF₂ P421 H Cl CH₃ H CF₃ H CH₃ O CH₂ O CH₂CHF₂ P422 H Cl CH₃ H CF₃ CF₃ Br O CH₂ O CH₂CF₃ P423 H Cl CH₃ H CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P424 H Cl CH₃ H CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P425 H Cl CH₃ H CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P426 H Cl CH₃ H CF₂CF₃ H Br O CH₂ O CH₂CF₃ P427 H Cl CH₃ H CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P428 H Cl CH₃ H CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P429 H Cl CH₃ H CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P430 H Cl CH₃ H CF₃ H Br O CH₂ O CH(CH₃)CF₃ P431 H Cl CH₃ H CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P432 H Cl CH₃ H CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P433 H Cl CH₃ H CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P434 H Cl CH₃ H CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P435 H Cl CH₃ H CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P436 H Cl CH₃ H CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P437 H Cl CH₃ H CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P438 H Cl CH₃ H CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P439 H Cl CH₃ H CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P440 H Cl CH₃ H CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P441 H Cl CH₃ H CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P442 H Cl CH₃ H CF₃ H Br O CH(CH₃) O CH₂CF₃ P443 H Cl CH₃ H CF₃ H Cl O CH (CH₃) O CH₂CF₃ P444 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P445 H Cl CH₃ H CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P446 H Cl CH₃ H CF₃ H Br O CH(CH₃) S CH₂CF₃ P447 H Cl CH₃ H CF₃ H Cl O CH (CH₃) S CH₂CF₃ P448 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P449 H Cl CH₃ H CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P450 H Cl CH₃ H CF₃ H Br S CH(CH₃) O CH₂CF₃ P451 H Cl CH₃ H CF₃ H Cl S CH (CH₃) O CH₂CF₃ P452 H Cl CH₃ H CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P453 H Cl CH₃ H CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P454 H Cl CH₃ H CF₃ H Br O CH(CH₃) O CH₂CHF₂ P455 H Cl CH₃ H CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P456 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P457 H Cl CH₃ H CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P458 H Cl CH₃ H CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P459 H Cl CH₃ H CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P460 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P461 H Cl CH₃ H CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P462 H Cl CH₃ H CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P463 H Cl CH₃ H CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P464 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P465 H Cl CH₃ H CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P466 H Cl CH₃ H CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P467 H Cl CH₃ H CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P468 H Cl CH₃ H CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P469 H Cl CH₃ H CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P470 H Cl CH₃ H CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P471 H Cl CH₃ H CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P472 H Cl CH₃ H CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P473 H Cl CH₃ H CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P474 H Cl CH₃ H CF₃ H Br O CH₂CH₂ O CH₂CF₃ P475 H Cl CH₃ H CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P476 H Cl CH₃ H CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P477 H Cl CH₃ H CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P478 H CH₃ F CH₃ CF₃ H Br O CH₂ O CH₂CF₃ P479 H CH₃ F CH₃ CF₃ H Cl O CH₂ O CH₂CF₃ P480 H CH₃ F CH₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P481 H CH₃ F CH₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P482 H CH₃ F CH₃ CF₃ H Br O CH₂ S CH₂CF₃ P483 H CH₃ F CH₃ CF₃ H Cl O CH₂ S CH₂CF₃ P484 H CH₃ F CH₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P485 H CH₃ F CH₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P486 H CH₃ F CH₃ CF₃ H Br S CH₂ O CH₂CF₃ P487 H CH₃ F CH₃ CF₃ H Cl S CH₂ O CH₂CF₃ P488 H CH₃ F CH₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P489 H CH₃ F CH₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P490 H CH₃ F CH₃ CF₃ H Br O CH₂ O CH₂CHF₂ P491 H CH₃ F CH₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P492 H CH₃ F CH₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P493 H CH₃ F CH₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P494 H CH₃ F CH₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P495 H CH₃ F CH₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P496 H CH₃ F CH₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P497 H CH₃ F CH₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P498 H CH₃ F CH₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P499 H CH₃ F CH₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P500 H CH₃ F CH₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P501 H CH₃ F CH₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P502 H CH₃ F CH₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P503 H CH₃ F CH₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P504 H CH₃ F CH₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P505 H CH₃ F CH₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P506 H CH₃ F CH₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P507 H CH₃ F CH₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P508 H CH₃ F CH₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P509 H CH₃ F CH₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P510 H CH₃ F CH₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P511 H CH₃ F CH₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P512 H CH₃ F CH₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P513 H CH₃ F CH₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P514 H CH₃ F CH₃ CF₃ H Br O CH(CH₃) O CH₂CF₃ P515 H CH₃ F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P516 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P517 H CH₃ F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P518 H CH₃ F CH₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P519 H CH₃ F CH₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P520 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P521 H CH₃ F CH₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P522 H CH₃ F CH₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P523 H CH₃ F CH₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P524 H CH₃ F CH₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P525 H CH₃ F CH₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P526 H CH₃ F CH₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P527 H CH₃ F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P528 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P529 H CH₃ F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P530 H CH₃ F CH₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P531 H CH₃ F CH₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P532 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P533 H CH₃ F CH₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P534 H CH₃ F CH₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P535 H CH₃ F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P536 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P537 H CH₃ F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P538 H CH₃ F CH₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P539 H CH₃ F CH₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P540 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P541 H CH₃ F CH₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P542 H CH₃ F CH₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P543 H CH₃ F CH₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P544 H CH₃ F CH₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P545 H CH₃ F CH₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P546 H CH₃ F CH₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P547 H CH₃ F CH₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P548 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P549 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P550 H Cl H Br CF₃ H Br O CH₂ O CH₂CF₃ P551 H Cl H Br CF₃ H Cl O CH₂ O CH₂CF₃ P552 H Cl H Br CF₃ H CF₃ O CH₂ O CH₂CF₃ P553 H Cl H Br CF₃ H CH₃ O CH₂ O CH₂CF₃ P554 H Cl H Br CF₃ H Br O CH₂ S CH₂CF₃ P555 H Cl H Br CF₃ H Cl O CH₂ S CH₂CF₃ P556 H Cl H Br CF₃ H CF₃ O CH₂ S CH₂CF₃ P557 H Cl H Br CF₃ H CH₃ O CH₂ S CH₂CF₃ P558 H Cl H Br CF₃ H Br S CH₂ O CH₂CF₃ P559 H Cl H Br CF₃ H Cl S CH₂ O CH₂CF₃ P560 H Cl H Br CF₃ H CF₃ S CH₂ O CH₂CF₃ P561 H Cl H Br CF₃ H CH₃ S CH₂ O CH₂CF₃ P562 H Cl H Br CF₃ H Br O CH₂ O CH₂CHF₂ P563 H Cl H Br CF₃ H Cl O CH₂ O CH₂CHF₂ P564 H Cl H Br CF₃ H CF₃ O CH₂ O CH₂CHF₂ P565 H Cl H Br CF₃ H CH₃ O CH₂ O CH₂CHF₂ P566 H Cl H Br CF₃ CF₃ Br O CH₂ O CH₂CF₃ P567 H Cl H Br CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P568 H Cl H Br CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P569 H Cl H Br CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P570 H Cl H Br CF₂CF₃ H Br O CH₂ O CH₂CF₃ P571 H Cl H Br CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P572 H Cl H Br CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P573 H Cl H Br CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P574 H Cl H Br CF₃ H Br O CH₂ O CH(CH₃)CF₃ P575 H Cl H Br CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P576 H Cl H Br CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P577 H Cl H Br CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P578 H Cl H Br CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P579 H Cl H Br CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P580 H Cl H Br CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P581 H Cl H Br CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P582 H Cl H Br CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P583 H Cl H Br CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P584 H Cl H Br CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P585 H Cl H Br CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P586 H Cl H Br CF₃ H Br O CH(CH₃) O CH₂CF₃ P587 H Cl H Br CF₃ H Cl O CH (CH₃) O CH₂CF₃ P588 H Cl H Br CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P589 H Cl H Br CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P590 H Cl H Br CF₃ H Br O CH(CH₃) S CH₂CF₃ P591 H Cl H Br CF₃ H Cl O CH (CH₃) S CH₂CF₃ P592 H Cl H Br CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P593 H Cl H Br CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P594 H Cl H Br CF₃ H Br S CH(CH₃) O CH₂CF₃ P595 H Cl H Br CF₃ H Cl S CH (CH₃) O CH₂CF₃ P596 H Cl H Br CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P597 H Cl H Br CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P598 H Cl H Br CF₃ H Br O CH(CH₃) O CH₂CHF₂ P599 H Cl H Br CF₃ H Cl O CH (CH₃) O CH2CHF₂ P600 H Cl H Br CF₃ H CF₃ O CH(CH₃) O CH2CHF₂ P601 H Cl H Br CF₃ H CH₃ O CH (CH₃) O CH2CHF₂ P602 H Cl H Br CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P603 H Cl H Br CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P604 H Cl H Br CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P605 H Cl H Br CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P606 H Cl H Br CF₃ H Br O CH(CH₃) O CH2CH₂CF₃ P607 H Cl H Br CF₃ H Cl O CH (CH₃) O CH2CH₂CF₃ P608 H Cl H Br CF₃ H CF₃ O CH(CH₃) O CH2CH₂CF₃ P609 H Cl H Br CF₃ H CH₃ O CH (CH₃) O CH2CH₂CF₃ P610 H Cl H Br CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P611 H Cl H Br CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P612 H Cl H Br CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P613 H Cl H Br CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P614 H Cl H Br CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P615 H Cl H Br CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P616 H Cl H Br CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P617 H Cl H Br CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P618 H Cl H Br CF₃ H Br O CH₂CH₂ O CH₂CF₃ P619 H Cl H Br CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P620 H Cl H Br CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P621 H Cl H Br CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P622 H H Br Br CF₃ H Br O CH₂ O CH₂CF₃ P623 H H Br Br CF₃ H Cl O CH₂ O CH₂CF₃ P624 H H Br Br CF₃ H CF₃ O CH₂ O CH₂CF₃ P625 H H Br Br CF₃ H CH₃ O CH₂ O CH₂CF₃ P626 H H Br Br CF₃ H Br O CH₂ S CH₂CF₃ P627 H H Br Br CF₃ H Cl O CH₂ S CH₂CF₃ P628 H H Br Br CF₃ H CF₃ O CH₂ S CH₂CF₃ P629 H H Br Br CF₃ H CH₃ O CH₂ S CH₂CF₃ P630 H H Br Br CF₃ H Br S CH₂ O CH₂CF₃ P631 H H Br Br CF₃ H Cl S CH₂ O CH₂CF₃ P632 H H Br Br CF₃ H CF₃ S CH₂ O CH₂CF₃ P633 H H Br Br CF₃ H CH₃ S CH₂ O CH₂CF₃ P634 H H Br Br CF₃ H Br O CH₂ O CH₂CHF₂ P635 H H Br Br CF₃ H Cl O CH₂ O CH₂CHF₂ P636 H H Br Br CF₃ H CF₃ O CH₂ O CH₂CHF₂ P637 H H Br Br CF₃ H CH₃ O CH₂ O CH₂CHF₂ P638 H H Br Br CF₃ CF₃ Br O CH₂ O CH₂CF₃ P639 H H Br Br CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P640 H H Br Br CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P641 H H Br Br CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P642 H H Br Br CF₂CF₃ H Br O CH₂ O CH₂CF₃ P643 H H Br Br CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P644 H H Br Br CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P645 H H Br Br CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P646 H H Br Br CF₃ H Br O CH₂ O CH(CH₃)CF₃ P647 H H Br Br CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P648 H H Br Br CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P649 H H Br Br CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P650 H H Br Br CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P651 H H Br Br CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P652 H H Br Br CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P653 H H Br Br CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P654 H H Br Br CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P655 H H Br Br CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P656 H H Br Br CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P657 H H Br Br CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P658 H H Br Br CF₃ H Br O CH(CH₃) O CH₂CF₃ P659 H H Br Br CF₃ H Cl O CH (CH₃) O CH₂CF₃ P660 H H Br Br CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P661 H H Br Br CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P662 H H Br Br CF₃ H Br O CH(CH₃) S CH₂CF₃ P663 H H Br Br CF₃ H Cl O CH (CH₃) S CH₂CF₃ P664 H H Br Br CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P665 H H Br Br CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P666 H H Br Br CF₃ H Br S CH(CH₃) O CH₂CF₃ P667 H H Br Br CF₃ H Cl S CH (CH₃) O CH₂CF₃ P668 H H Br Br CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P669 H H Br Br CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P670 H H Br Br CF₃ H Br O CH(CH₃) O CH₂CHF₂ P671 H H Br Br CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P672 H H Br Br CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P673 H H Br Br CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P674 H H Br Br CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P675 H H Br Br CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P676 H H Br Br CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P677 H H Br Br CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P678 H H Br Br CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P679 H H Br Br CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P680 H H Br Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P681 H H Br Br CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P682 H H Br Br CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P683 H H Br Br CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P684 H H Br Br CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P685 H H Br Br CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P686 H H Br Br CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P687 H H Br Br CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P688 H H Br Br CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P689 H H Br Br CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P690 H H Br Br CF₃ H Br O CH₂CH₂ O CH₂CF₃ P691 H H Br Br CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P692 H H Br Br CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P693 H H Br Br CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P694 H H Cl NO₂ CF₃ H Br O CH₂ O CH₂CF₃ P695 H H Cl NO₂ CF₃ H Cl O CH₂ O CH₂CF₃ P696 H H Cl NO₂ CF₃ H CF₃ O CH₂ O CH₂CF₃ P697 H H Cl NO₂ CF₃ H CH₃ O CH₂ O CH₂CF₃ P698 H H Cl NO₂ CF₃ H Br O CH₂ S CH₂CF₃ P699 H H Cl NO₂ CF₃ H Cl O CH₂ S CH₂CF₃ P700 H H Cl NO₂ CF₃ H CF₃ O CH₂ S CH₂CF₃ P701 H H Cl NO₂ CF₃ H CH₃ O CH₂ S CH₂CF₃ P702 H H Cl NO₂ CF₃ H Br S CH₂ O CH₂CF₃ P703 H H Cl NO₂ CF₃ H Cl S CH₂ O CH₂CF₃ P704 H H Cl NO₂ CF₃ H CF₃ S CH₂ O CH₂CF₃ P705 H H Cl NO₂ CF₃ H CH₃ S CH₂ O CH₂CF₃ P706 H H Cl NO₂ CF₃ H Br O CH₂ O CH₂CHF₂ P707 H H Cl NO₂ CF₃ H Cl O CH₂ O CH₂CHF₂ P708 H H Cl NO₂ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P709 H H Cl NO₂ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P710 H H Cl NO₂ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P711 H H Cl NO₂ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P712 H H Cl NO₂ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P713 H H Cl NO₂ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P714 H H Cl NO₂ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P715 H H Cl NO₂ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P716 H H Cl NO₂ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P717 H H Cl NO₂ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P718 H H Cl NO₂ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P719 H H Cl NO₂ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P720 H H Cl NO₂ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P721 H H Cl NO₂ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P722 H H Cl NO₂ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P723 H H Cl NO₂ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P724 H H Cl NO₂ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P725 H H Cl NO₂ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P726 H H Cl NO₂ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P727 H H Cl NO₂ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P728 H H Cl NO₂ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P729 H H Cl NO₂ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P730 H H Cl NO₂ CF₃ H Br O CH(CH₃) O CH₂CF₃ P731 H H Cl NO₂ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P732 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P733 H H Cl NO₂ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P734 H H Cl NO₂ CF₃ H Br O CH(CH₃) S CH₂CF₃ P735 H H Cl NO₂ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P736 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P737 H H Cl NO₂ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P738 H H Cl NO₂ CF₃ H Br S CH(CH₃) O CH₂CF₃ P739 H H Cl NO₂ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P740 H H Cl NO₂ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P741 H H Cl NO₂ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P742 H H Cl NO₂ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P743 H H Cl NO₂ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P744 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P745 H H Cl NO₂ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P746 H H Cl NO₂ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P747 H H Cl NO₂ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P748 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P749 H H Cl NO₂ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P750 H H Cl NO₂ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P751 H H Cl NO₂ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P752 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P753 H H Cl NO₂ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P754 H H Cl NO₂ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P755 H H Cl NO₂ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P756 H H Cl NO₂ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P757 H H Cl NO₂ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P758 H H Cl NO₂ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P759 H H Cl NO₂ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P760 H H Cl NO₂ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P761 H H Cl NO₂ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P762 H H Cl NO₂ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P763 H H Cl NO₂ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P764 H H Cl NO₂ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P765 H H Cl NO₂ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P766 H H F CN CF₃ H Br O CH₂ O CH₂CF₃ P767 H H F CN CF₃ H Cl O CH₂ O CH₂CF₃ P768 H H F CN CF₃ H CF₃ O CH₂ O CH₂CF₃ P769 H H F CN CF₃ H CH₃ O CH₂ O CH₂CF₃ P770 H H F CN CF₃ H Br O CH₂ S CH₂CF₃ P771 H H F CN CF₃ H Cl O CH₂ S CH₂CF₃ P772 H H F CN CF₃ H CF₃ O CH₂ S CH₂CF₃ P773 H H F CN CF₃ H CH₃ O CH₂ S CH₂CF₃ P774 H H F CN CF₃ H Br S CH₂ O CH₂CF₃ P775 H H F CN CF₃ H Cl S CH₂ O CH₂CF₃ P776 H H F CN CF₃ H CF₃ S CH₂ O CH₂CF₃ P777 H H F CN CF₃ H CH₃ S CH₂ O CH₂CF₃ P778 H H F CN CF₃ H Br O CH₂ O CH₂CHF₂ P779 H H F CN CF₃ H Cl O CH₂ O CH₂CHF₂ P780 H H F CN CF₃ H CF₃ O CH₂ O CH₂CHF₂ P781 H H F CN CF₃ H CH₃ O CH₂ O CH₂CHF₂ P782 H H F CN CF₃ CF₃ Br O CH₂ O CH₂CF₃ P783 H H F CN CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P784 H H F CN CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P785 H H F CN CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P786 H H F CN CF₂CF₃ H Br O CH₂ O CH₂CF₃ P787 H H F CN CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P788 H H F CN CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P789 H H F CN CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P790 H H F CN CF₃ H Br O CH₂ O CH(CH₃)CF₃ P791 H H F CN CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P792 H H F CN CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P793 H H F CN CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P794 H H F CN CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P795 H H F CN CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P796 H H F CN CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P797 H H F CN CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P798 H H F CN CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P799 H H F CN CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P800 H H F CN CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P801 H H F CN CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P802 H H F CN CF₃ H Br O CH(CH₃) O CH₂CF₃ P803 H H F CN CF₃ H Cl O CH (CH₃) O CH₂CF₃ P804 H H F CN CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P805 H H F CN CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P806 H H F CN CF₃ H Br O CH(CH₃) S CH₂CF₃ P807 H H F CN CF₃ H Cl O CH (CH₃) S CH₂CF₃ P808 H H F CN CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P809 H H F CN CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P810 H H F CN CF₃ H Br S CH(CH₃) O CH₂CF₃ P811 H H F CN CF₃ H Cl S CH (CH₃) O CH₂CF₃ P812 H H F CN CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P813 H H F CN CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P814 H H F CN CF₃ H Br O CH(CH₃) O CH₂CHF₂ P815 H H F CN CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P816 H H F CN CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P817 H H F CN CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P818 H H F CN CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P819 H H F CN CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P820 H H F CN CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P821 H H F CN CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P822 H H F CN CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P823 H H F CN CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P824 H H F CN CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P825 H H F CN CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P826 H H F CN CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P827 H H F CN CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P828 H H F CN CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P829 H H F CN CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P830 H H F CN CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P831 H H F CN CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P832 H H F CN CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P833 H H F CN CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P834 H H F CN CF₃ H Br O CH₂CH₂ O CH₂CF₃ P835 H H F CN CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P836 H H F CN CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P837 H H F CN CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P838 H Cl OCF₃ Cl CF₃ H Br O CH₂ O CH₂CF₃ P839 H Cl OCF₃ Cl CF₃ H Cl O CH₂ O CH₂CF₃ P840 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P841 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂ O CH₂CF₃ P842 H Cl OCF₃ Cl CF₃ H Br O CH₂ S CH₂CF₃ P843 H Cl OCF₃ Cl CF₃ H Cl O CH₂ S CH₂CF₃ P844 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P845 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P846 H Cl OCF₃ Cl CF₃ H Br S CH₂ O CH₂CF₃ P847 H Cl OCF₃ Cl CF₃ H Cl S CH₂ O CH₂CF₃ P848 H Cl OCF₃ Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P849 H Cl OCF₃ Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P850 H Cl OCF₃ Cl CF₃ H Br O CH₂ O CH₂CHF₂ P851 H Cl OCF₃ Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P852 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P853 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P854 H Cl OCF₃ Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P855 H Cl OCF₃ Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P856 H Cl OCF₃ Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P857 H Cl OCF₃ Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P858 H Cl OCF₃ Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P859 H Cl OCF₃ Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P860 H Cl OCF₃ Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P861 H Cl OCF₃ Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P862 H Cl OCF₃ Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P863 H Cl OCF₃ Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P864 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P865 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P866 H Cl OCF₃ Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P867 H Cl OCF₃ Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P868 H Cl OCF₃ Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P869 H Cl OCF₃ Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P870 H Cl OCF₃ Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P871 H Cl OCF₃ Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P872 H Cl OCF₃ Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P873 H Cl OCF₃ Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P874 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P875 H Cl OCF₃ Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P876 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P877 H Cl OCF₃ Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P878 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P879 H Cl OCF₃ Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P880 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P881 H Cl OCF₃ Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P882 H Cl OCF₃ Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P883 H Cl OCF₃ Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P884 H Cl OCF₃ Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P885 H Cl OCF₃ Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P886 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P887 H Cl OCF₃ Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P888 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P889 H Cl OCF₃ Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P890 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P891 H Cl OCF₃ Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P892 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P893 H Cl OCF₃ Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P894 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P895 H Cl OCF₃ Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P896 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P897 H Cl OCF₃ Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P898 H Cl OCF₃ Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P899 H Cl OCF₃ Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P900 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P901 H Cl OCF₃ Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P902 H Cl OCF₃ Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P903 H Cl OCF₃ Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P904 H Cl OCF₃ Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P905 H Cl OCF₃ Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P906 H Cl OCF₃ Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P907 H Cl OCF₃ Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P908 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P909 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P910 H Cl CN Cl CF₃ H Br O CH₂ O CH₂CF₃ P911 H Cl CN Cl CF₃ H Cl O CH₂ O CH₂CF₃ P912 H Cl CN Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P913 H Cl CN Cl CF₃ H CH₃ O CH₂ O CH₂CF₃ P914 H Cl CN Cl CF₃ H Br O CH₂ S CH₂CF₃ P915 H Cl CN Cl CF₃ H Cl O CH₂ S CH₂CF₃ P916 H Cl CN Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P917 H Cl CN Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P918 H Cl CN Cl CF₃ H Br S CH₂ O CH₂CF₃ P919 H Cl CN Cl CF₃ H Cl S CH₂ O CH₂CF₃ P920 H Cl CN Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P921 H Cl CN Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P922 H Cl CN Cl CF₃ H Br O CH₂ O CH₂CHF₂ P923 H Cl CN Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P924 H Cl CN Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P925 H Cl CN Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P926 H Cl CN Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P927 H Cl CN Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P928 H Cl CN Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P929 H Cl CN Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P930 H Cl CN Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P931 H Cl CN Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P932 H Cl CN Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P933 H Cl CN Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P934 H Cl CN Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P935 H Cl CN Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P936 H Cl CN Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P937 H Cl CN Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P938 H Cl CN Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P939 H Cl CN Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P940 H Cl CN Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P941 H Cl CN Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P942 H Cl CN Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P943 H Cl CN Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P944 H Cl CN Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P945 H Cl CN Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P946 H Cl CN Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P947 H Cl CN Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P948 H Cl CN Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P949 H Cl CN Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P950 H Cl CN Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P951 H Cl CN Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P952 H Cl CN Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P953 H Cl CN Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P954 H Cl CN Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P955 H Cl CN Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P956 H Cl CN Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P957 H Cl CN Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P958 H Cl CN Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P959 H Cl CN Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P960 H Cl CN Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P961 H Cl CN Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P962 H Cl CN Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P963 H Cl CN Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P964 H Cl CN Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P965 H Cl CN Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P966 H Cl CN Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P967 H Cl CN Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P968 H Cl CN Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P969 H Cl CN Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P970 H Cl CN Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P971 H Cl CN Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P972 H Cl CN Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P973 H Cl CN Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P974 H Cl CN Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P975 H Cl CN Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P976 H Cl CN Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P977 H Cl CN Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P978 H Cl CN Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P979 H Cl CN Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P980 H Cl CN Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P981 H Cl CN Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P982 H CH₃ H Br CF₃ H Br O CH₂ O CH₂CF₃ P983 H CH₃ H Br CF₃ H Cl O CH₂ O CH₂CF₃ P984 H CH₃ H Br CF₃ H CF₃ O CH₂ O CH₂CF₃ P985 H CH₃ H Br CF₃ H CH₃ O CH₂ O CH₂CF₃ P986 H CH₃ H Br CF₃ H Br O CH₂ S CH₂CF₃ P987 H CH₃ H Br CF₃ H Cl O CH₂ S CH₂CF₃ P988 H CH₃ H Br CF₃ H CF₃ O CH₂ S CH₂CF₃ P989 H CH₃ H Br CF₃ H CH₃ O CH₂ S CH₂CF₃ P990 H CH₃ H Br CF₃ H Br S CH₂ O CH₂CF₃ P991 H CH₃ H Br CF₃ H Cl S CH₂ O CH₂CF₃ P992 H CH₃ H Br CF₃ H CF₃ S CH₂ O CH₂CF₃ P993 H CH₃ H Br CF₃ H CH₃ S CH₂ O CH₂CF₃ P994 H CH₃ H Br CF₃ H Br O CH₂ O CH₂CHF₂ P995 H CH₃ H Br CF₃ H Cl O CH₂ O CH₂CHF₂ P996 H CH₃ H Br CF₃ H CF₃ O CH₂ O CH₂CHF₂ P997 H CH₃ H Br CF₃ H CH₃ O CH₂ O CH₂CHF₂ P998 H CH₃ H Br CF₃ CF₃ Br O CH₂ O CH₂CF₃ P999 H CH₃ H Br CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1000 H CH₃ H Br CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1001 H CH₃ H Br CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1002 H CH₃ H Br CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1003 H CH₃ H Br CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1004 H CH₃ H Br CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1005 H CH₃ H Br CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1006 H CH₃ H Br CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1007 H CH₃ H Br CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1008 H CH₃ H Br CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1009 H CH₃ H Br CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1010 H CH₃ H Br CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1011 H CH₃ H Br CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1012 H CH₃ H Br CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1013 H CH₃ H Br CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1014 H CH₃ H Br CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1015 H CH₃ H Br CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1016 H CH₃ H Br CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1017 H CH₃ H Br CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1018 H CH₃ H Br CF₃ H Br O CH(CH₃) O CH₂CF₃ P1019 H CH₃ H Br CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1020 H CH₃ H Br CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1021 H CH₃ H Br CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1022 H CH₃ H Br CF₃ H Br O CH(CH₃) S CH₂CF₃ P1023 H CH₃ H Br CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1024 H CH₃ H Br CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1025 H CH₃ H Br CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1026 H CH₃ H Br CF₃ H Br S CH(CH₃) O CH₂CF₃ P1027 H CH₃ H Br CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1028 H CH₃ H Br CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1029 H CH₃ H Br CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1030 H CH₃ H Br CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1031 H CH₃ H Br CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1032 H CH₃ H Br CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1033 H CH₃ H Br CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1034 H CH₃ H Br CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1035 H CH₃ H Br CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1036 H CH₃ H Br CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1037 H CH₃ H Br CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1038 H CH₃ H Br CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1039 H CH₃ H Br CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1040 H CH₃ H Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1041 H CH₃ H Br CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1042 H CH₃ H Br CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1043 H CH₃ H Br CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1044 H CH₃ H Br CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1045 H CH₃ H Br CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1046 H CH₃ H Br CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1047 H CH₃ H Br CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1048 H CH₃ H Br CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1049 H CH₃ H Br CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1050 H CH₃ H Br CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1051 H CH₃ H Br CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1052 H CH₃ H Br CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1053 H CH₃ H Br CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1054 H H F CH₃ CF₃ H Br O CH₂ O CH₂CF₃ P1055 H H F CH₃ CF₃ H Cl O CH₂ O CH₂CF₃ P1056 H H F CH₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P1057 H H F CH₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P1058 H H F CH₃ CF₃ H Br O CH₂ S CH₂CF₃ P1059 H H F CH₃ CF₃ H Cl O CH₂ S CH₂CF₃ P1060 H H F CH₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P1061 H H F CH₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P1062 H H F CH₃ CF₃ H Br S CH₂ O CH₂CF₃ P1063 H H F CH₃ CF₃ H Cl S CH₂ O CH₂CF₃ P1064 H H F CH₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P1065 H H F CH₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P1066 H H F CH₃ CF₃ H Br O CH₂ O CH₂CHF₂ P1067 H H F CH₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P1068 H H F CH₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1069 H H F CH₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1070 H H F CH₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1071 H H F CH₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1072 H H F CH₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1073 H H F CH₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1074 H H F CH₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1075 H H F CH₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1076 H H F CH₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1077 H H F CH₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1078 H H F CH₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1079 H H F CH₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1080 H H F CH₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1081 H H F CH₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1082 H H F CH₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1083 H H F CH₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1084 H H F CH₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1085 H H F CH₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1086 H H F CH₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1087 H H F CH₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1088 H H F CH₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1089 H H F CH₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1090 H H F CH₃ CF₃ H Br O CH(CH₃) O CH₂CF₃ P1091 H H F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1092 H H F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1093 H H F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1094 H H F CH₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P1095 H H F CH₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1096 H H F CH₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1097 H H F CH₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1098 H H F CH₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P1099 H H F CH₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1100 H H F CH₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1101 H H F CH₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1102 H H F CH₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1103 H H F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1104 H H F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1105 H H F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1106 H H F CH₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1107 H H F CH₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1108 H H F CH₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1109 H H F CH₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1110 H H F CH₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1111 H H F CH₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1112 H H F CH₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1113 H H F CH₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1114 H H F CH₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1115 H H F CH₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1116 H H F CH₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1117 H H F CH₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1118 H H F CH₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1119 H H F CH₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1120 H H F CH₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1121 H H F CH₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1122 H H F CH₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1123 H H F CH₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1124 H H F CH₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1125 H H F CH₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1126 H H F Cl CF₃ H Cl O CH₂ O CH₂CF₃ P1127 H H F Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P1128 H H F Cl CF₃ H CH₃ O CH₂ O CH₂CF₃ P1129 H H F Cl CF₃ H Br O CH₂ S CH₂CF₃ P1130 H H F Cl CF₃ H Cl O CH₂ S CH₂CF₃ P1131 H H F Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P1132 H H F Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P1133 H H F Cl CF₃ H Br S CH₂ O CH₂CF₃ P1134 H H F Cl CF₃ H Cl S CH₂ O CH₂CF₃ P1135 H H F Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P1136 H H F Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P1137 H H F Cl CF₃ H Br O CH₂ O CH₂CHF₂ P1138 H H F Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P1139 H H F Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1140 H H F Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1141 H H F Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1142 H H F Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1143 H H F Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1144 H H F Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1145 H H F Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1146 H H F Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1147 H H F Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1148 H H F Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1149 H H F Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1150 H H F Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1151 H H F Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1152 H H F Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1153 H H F Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1154 H H F Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1155 H H F Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1156 H H F Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1157 H H F Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1158 H H F Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1159 H H F Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1160 H H F Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1161 H H F Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P1162 H H F Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1163 H H F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1164 H H F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1165 H H F Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P1166 H H F Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1167 H H F Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1168 H H F Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1169 H H F Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P1170 H H F Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1171 H H F Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1172 H H F Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1173 H H F Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1174 H H F Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1175 H H F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1176 H H F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1177 H H F Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1178 H H F Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1179 H H F Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1180 H H F Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1181 H H F Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1182 H H F Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1183 H H F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1184 H H F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1185 H H F Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1186 H H F Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1187 H H F Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1188 H H F Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1189 H H F Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1190 H H F Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1191 H H F Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1192 H H F Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1193 H H F Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1194 H H F Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1195 H H F Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1196 H H F Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1197 H F F F CF₃ H Br O CH₂ O CH₂CF₃ P1198 H F F F CF₃ H Cl O CH₂ O CH₂CF₃ P1199 H F F F CF₃ H CF₃ O CH₂ O CH₂CF₃ P1200 H F F F CF₃ H CH₃ O CH₂ O CH₂CF₃ P1201 H F F F CF₃ H Br O CH₂ S CH₂CF₃ P1202 H F F F CF₃ H Cl O CH₂ S CH₂CF₃ P1203 H F F F CF₃ H CF₃ O CH₂ S CH₂CF₃ P1204 H F F F CF₃ H CH₃ O CH₂ S CH₂CF₃ P1205 H F F F CF₃ H Br S CH₂ O CH₂CF₃ P1206 H F F F CF₃ H Cl S CH₂ O CH₂CF₃ P1207 H F F F CF₃ H CF₃ S CH₂ O CH₂CF₃ P1208 H F F F CF₃ H CH₃ S CH₂ O CH₂CF₃ P1209 H F F F CF₃ H Br O CH₂ O CH₂CHF₂ P1210 H F F F CF₃ H Cl O CH₂ O CH₂CHF₂ P1211 H F F F CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1212 H F F F CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1213 H F F F CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1214 H F F F CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1215 H F F F CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1216 H F F F CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1217 H F F F CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1218 H F F F CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1219 H F F F CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1220 H F F F CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1221 H F F F CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1222 H F F F CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1223 H F F F CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1224 H F F F CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1225 H F F F CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1226 H F F F CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1227 H F F F CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1228 H F F F CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1229 H F F F CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1230 H F F F CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1231 H F F F CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1232 H F F F CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1233 H F F F CF₃ H Br O CH(CH₃) O CH₂CF₃ P1234 H F F F CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1235 H F F F CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1236 H F F F CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1237 H F F F CF₃ H Br O CH(CH₃) S CH₂CF₃ P1238 H F F F CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1239 H F F F CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1240 H F F F CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1241 H F F F CF₃ H Br S CH(CH₃) O CH₂CF₃ P1242 H F F F CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1243 H F F F CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1244 H F F F CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1245 H F F F CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1246 H F F F CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1247 H F F F CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1248 H F F F CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1249 H F F F CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1250 H F F F CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1251 H F F F CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1252 H F F F CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1253 H F F F CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1254 H F F F CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1255 H F F F CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1256 H F F F CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1257 H F F F CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1258 H F F F CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1259 H F F F CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1260 H F F F CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1261 H F F F CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1262 H F F F CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1263 H F F F CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1264 H F F F CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1265 H F F F CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1266 H F F F CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1267 H F F F CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1268 H F F F CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1269 H CF₃ H CF₃ CF₃ H Br O CH₂ O CH₂CF₃ P1270 H CF₃ H CF₃ CF₃ H Cl O CH₂ O CH₂CF₃ P1271 H CF₃ H CF₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P1272 H CF₃ H CF₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P1273 H CF₃ H CF₃ CF₃ H Br O CH₂ S CH₂CF₃ P1274 H CF₃ H CF₃ CF₃ H Cl O CH₂ S CH₂CF₃ P1275 H CF₃ H CF₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P1276 H CF₃ H CF₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P1277 H CF₃ H CF₃ CF₃ H Br S CH₂ O CH₂CF₃ P1278 H CF₃ H CF₃ CF₃ H Cl S CH₂ O CH₂CF₃ P1279 H CF₃ H CF₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P1280 H CF₃ H CF₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P1281 H CF₃ H CF₃ CF₃ H Br O CH₂ O CH₂CHF₂ P1282 H CF₃ H CF₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P1283 H CF₃ H CF₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1284 H CF₃ H CF₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1285 H CF₃ H CF₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1286 H CF₃ H CF₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1287 H CF₃ H CF₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1288 H CF₃ H CF₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1289 H CF₃ H CF₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1290 H CF₃ H CF₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1291 H CF₃ H CF₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1292 H CF₃ H CF₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1293 H CF₃ H CF₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1294 H CF₃ H CF₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1295 H CF₃ H CF₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1296 H CF₃ H CF₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1297 H CF₃ H CF₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1298 H CF₃ H CF₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1299 H CF₃ H CF₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1300 H CF₃ H CF₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1301 H CF₃ H CF₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1302 H CF₃ H CF₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1303 H CF₃ H CF₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1304 H CF₃ H CF₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1305 H CF₃ H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1306 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1307 H CF₃ H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1308 H CF₃ H CF₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P1309 H CF₃ H CF₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1310 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1311 H CF₃ H CF₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1312 H CF₃ H CF₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P1313 H CF₃ H CF₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1314 H CF₃ H CF₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1315 H CF₃ H CF₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1316 H CF₃ H CF₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1317 H CF₃ H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1318 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1319 H CF₃ H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1320 H CF₃ H CF₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1321 H CF₃ H CF₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1322 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1323 H CF₃ H CF₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1324 H CF₃ H CF₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1325 H CF₃ H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1326 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1327 H CF₃ H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1328 H CF₃ H CF₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1329 H CF₃ H CF₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1330 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1331 H CF₃ H CF₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1332 H CF₃ H CF₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1333 H CF₃ H CF₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1334 H CF₃ H CF₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1335 H CF₃ H CF₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1336 H CF₃ H CF₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1337 H CF₃ H CF₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1338 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1339 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1340 H F H CF₃ CF₃ H Br O CH₂ O CH₂CF₃ P1341 H F H CF₃ CF₃ H Cl O CH₂ O CH₂CF₃ P1342 H F H CF₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P1343 H F H CF₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P1344 H F H CF₃ CF₃ H Br O CH₂ S CH₂CF₃ P1345 H F H CF₃ CF₃ H Cl O CH₂ S CH₂CF₃ P1346 H F H CF₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P1347 H F H CF₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P1348 H F H CF₃ CF₃ H Br S CH₂ O CH₂CF₃ P1349 H F H CF₃ CF₃ H Cl S CH₂ O CH₂CF₃ P1350 H F H CF₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P1351 H F H CF₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P1352 H F H CF₃ CF₃ H Br O CH₂ O CH₂CHF₂ P1353 H F H CF₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P1354 H F H CF₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1355 H F H CF₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1356 H F H CF₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1357 H F H CF₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1358 H F H CF₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1359 H F H CF₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1360 H F H CF₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1361 H F H CF₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1362 H F H CF₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1363 H F H CF₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1364 H F H CF₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1365 H F H CF₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1366 H F H CF₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1367 H F H CF₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1368 H F H CF₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1369 H F H CF₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1370 H F H CF₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1371 H F H CF₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1372 H F H CF₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1373 H F H CF₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1374 H F H CF₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1375 H F H CF₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1376 H F H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1377 H F H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1378 H F H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1379 H F H CF₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P1380 H F H CF₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1381 H F H CF₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1382 H F H CF₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1383 H F H CF₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P1384 H F H CF₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1385 H F H CF₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1386 H F H CF₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1387 H F H CF₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1388 H F H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1389 H F H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1390 H F H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1391 H F H CF₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1392 H F H CF₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1393 H F H CF₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1394 H F H CF₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1395 H F H CF₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1396 H F H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1397 H F H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1398 H F H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1399 H F H CF₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1400 H F H CF₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1401 H F H CF₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1402 H F H CF₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1403 H F H CF₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1404 H F H CF₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1405 H F H CF₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1406 H F H CF₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1407 H F H CF₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1408 H F H CF₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1409 H F H CF₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1410 H F H CF₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1411 H Cl H CF₃ CF₃ H Br O CH₂ O CH₂CF₃ P1412 H Cl H CF₃ CF₃ H Cl O CH₂ O CH₂CF₃ P1413 H Cl H CF₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P1414 H Cl H CF₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P1415 H Cl H CF₃ CF₃ H Br O CH₂ S CH₂CF₃ P1416 H Cl H CF₃ CF₃ H Cl O CH₂ S CH₂CF₃ P1417 H Cl H CF₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P1418 H Cl H CF₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P1419 H Cl H CF₃ CF₃ H Br S CH₂ O CH₂CF₃ P1420 H Cl H CF₃ CF₃ H Cl S CH₂ O CH₂CF₃ P1421 H Cl H CF₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P1422 H Cl H CF₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P1423 H Cl H CF₃ CF₃ H Br O CH₂ O CH₂CHF₂ P1424 H Cl H CF₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P1425 H Cl H CF₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1426 H Cl H CF₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1427 H Cl H CF₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1428 H Cl H CF₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1429 H Cl H CF₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1430 H Cl H CF₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1431 H Cl H CF₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1432 H Cl H CF₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1433 H Cl H CF₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1434 H Cl H CF₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1435 H Cl H CF₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1436 H Cl H CF₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1437 H Cl H CF₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1438 H Cl H CF₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1439 H Cl H CF₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1440 H Cl H CF₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1441 H Cl H CF₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1442 H Cl H CF₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1443 H Cl H CF₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1444 H Cl H CF₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1445 H Cl H CF₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1446 H Cl H CF₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1447 H Cl H CF₃ CF₃ H Br O CH(CH₃) O CH₂CF₃ P1448 H Cl H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1449 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1450 H Cl H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1451 H Cl H CF₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P1452 H Cl H CF₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1453 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1454 H Cl H CF₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1455 H Cl H CF₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P1456 H Cl H CF₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1457 H Cl H CF₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1458 H Cl H CF₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1459 H Cl H CF₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1460 H Cl H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1461 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1462 H Cl H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1463 H Cl H CF₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1464 H Cl H CF₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1465 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1466 H Cl H CF₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1467 H Cl H CF₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1468 H Cl H CF₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1469 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1470 H Cl H CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1471 H Cl H CF₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1472 H Cl H CF₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1473 H Cl H CF₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1474 H Cl H CF₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1475 H Cl H CF₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1476 H Cl H CF₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1477 H Cl H CF₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1478 H Cl H CF₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1479 H Cl H CF₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1480 H Cl H CF₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1481 H Cl H CF₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1482 H Cl H CF₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1483 H H F CF₃ CF₃ H Br O CH₂ O CH₂CF₃ P1484 H H F CF₃ CF₃ H Cl O CH₂ O CH₂CF₃ P1485 H H F CF₃ CF₃ H CF₃ O CH₂ O CH₂CF₃ P1486 H H F CF₃ CF₃ H CH₃ O CH₂ O CH₂CF₃ P1487 H H F CF₃ CF₃ H Br O CH₂ S CH₂CF₃ P1488 H H F CF₃ CF₃ H Cl O CH₂ S CH₂CF₃ P1489 H H F CF₃ CF₃ H CF₃ O CH₂ S CH₂CF₃ P1490 H H F CF₃ CF₃ H CH₃ O CH₂ S CH₂CF₃ P1491 H H F CF₃ CF₃ H Br S CH₂ O CH₂CF₃ P1492 H H F CF₃ CF₃ H Cl S CH₂ O CH₂CF₃ P1493 H H F CF₃ CF₃ H CF₃ S CH₂ O CH₂CF₃ P1494 H H F CF₃ CF₃ H CH₃ S CH₂ O CH₂CF₃ P1495 H H F CF₃ CF₃ H Br O CH₂ O CH₂CHF₂ P1496 H H F CF₃ CF₃ H Cl O CH₂ O CH₂CHF₂ P1497 H H F CF₃ CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1498 H H F CF₃ CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1499 H H F CF₃ CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1500 H H F CF₃ CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1501 H H F CF₃ CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1502 H H F CF₃ CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1503 H H F CF₃ CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1504 H H F CF₃ CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1505 H H F CF₃ CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1506 H H F CF₃ CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1507 H H F CF₃ CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1508 H H F CF₃ CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1509 H H F CF₃ CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1510 H H F CF₃ CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1511 H H F CF₃ CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1512 H H F CF₃ CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1513 H H F CF₃ CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1514 H H F CF₃ CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1515 H H F CF₃ CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1516 H H F CF₃ CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1517 H H F CF₃ CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1518 H H F CF₃ CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1519 H H F CF₃ CF₃ H Br O CH(CH₃) O CH₂CF₃ P1520 H H F CF₃ CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1521 H H F CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1522 H H F CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1523 H H F CF₃ CF₃ H Br O CH(CH₃) S CH₂CF₃ P1524 H H F CF₃ CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1525 H H F CF₃ CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1526 H H F CF₃ CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1527 H H F CF₃ CF₃ H Br S CH(CH₃) O CH₂CF₃ P1528 H H F CF₃ CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1529 H H F CF₃ CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1530 H H F CF₃ CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1531 H H F CF₃ CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1532 H H F CF₃ CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1533 H H F CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1534 H H F CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1535 H H F CF₃ CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1536 H H F CF₃ CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1537 H H F CF₃ CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1538 H H F CF₃ CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1539 H H F CF₃ CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1540 H H F CF₃ CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1541 H H F CF₃ CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1542 H H F CF₃ CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1543 H H F CF₃ CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1544 H H F CF₃ CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1545 H H F CF₃ CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1546 H H F CF₃ CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1547 H H F CF₃ CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1548 H H F CF₃ CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1549 H H F CF₃ CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1550 H H F CF₃ CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1551 H H F CF₃ CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1552 H H F CF₃ CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1553 H H F CF₃ CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1554 H H F CF₃ CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1555 H Cl Cl Cl CF₃ H H O CH₂ O CH₂CF₃ P1556 H Cl Cl Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P1557 H Cl Cl Cl CF₃ H H O CH₂ S CH₂CF₃ P1558 H Cl Cl Cl CF₃ H Cl O CH₂ S CH₂CF₃ P1559 H Cl Cl Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P1560 H Cl Cl Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P1561 H Cl Cl Cl CF₃ H H S CH₂ O CH₂CF₃ P1562 H Cl Cl Cl CF₃ H Cl S CH₂ O CH₂CF₃ P1563 H Cl Cl Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P1564 H Cl Cl Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P1565 H Cl Cl Cl CF₃ H H O CH₂ O CH₂CHF₂ P1566 H Cl Cl Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1567 H Cl Cl Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1568 H Cl Cl Cl CF₃ H H O CH₂ O CH₂CH₂F P1569 H Cl Cl Cl CF₃ H Br O CH₂ O CH₂CH₂F P1570 H Cl Cl Cl CF₃ H Cl O CH₂ O CH₂CH₂F P1571 H Cl Cl Cl CF₃ H CF₃ O CH₂ O CH₂CH₂F P1572 H Cl Cl Cl CF₃ H CH₃ O CH₂ O CH₂CH₂F P1573 H Cl Cl Cl CF₃ H H O CH₂ O CH₂CH₃ P1574 H Cl Cl Cl CF₃ H Br O CH₂ O CH₂CH₃ P1575 H Cl Cl Cl CF₃ H Cl O CH₂ O CH₂CH₃ P1576 H Cl Cl Cl CF₃ H CF₃ O CH₂ O CH₂CH₃ P1577 H Cl Cl Cl CF₃ H CH₃ O CH₂ O CH₂CH₃ P1578 H Cl Cl Cl CF₃ CF₃ H O CH₂ O CH₂CF₃ P1579 H Cl Cl Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1580 H Cl Cl Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1581 H Cl Cl Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1582 H Cl Cl Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1583 H Cl Cl Cl CF₂CF₃ H H O CH₂ O CH₂CF₃ P1584 H Cl Cl Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1585 H Cl Cl Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1586 H Cl Cl Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1587 H Cl Cl Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1588 H Cl Cl Cl CF₃ H H O CH₂ O CH(CH₃)CF₃ P1589 H Cl Cl Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1590 H Cl Cl Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1591 H Cl Cl Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1592 H Cl Cl Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1593 H Cl Cl Cl CF₃ CF₃ H O CH(CH₃) O CH₂CF₃ P1594 H Cl Cl Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1595 H Cl Cl Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1596 H Cl Cl Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1597 H Cl Cl Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1598 H Cl Cl Cl CF₂CF₃ H H O CH (CH₃) O CH₂CF₃ P1599 H Cl Cl Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1600 H Cl Cl Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1601 H Cl Cl Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1602 H Cl Cl Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1603 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH₂CF₃ P1604 H Cl Cl Cl CF₃ H H O CH(CH₃) S CH₂CF₃ P1605 H Cl Cl Cl CF₃ H H S CH(CH₃) O CH₂CF₃ P1606 H Cl Cl Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P1607 H Cl Cl Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1608 H Cl Cl Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1609 H Cl Cl Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1610 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH₂CHF₂ P1611 H Cl Cl Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1612 H Cl Cl Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1613 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1614 H Cl Cl Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1615 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₂F P1616 H Cl Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₂F P1617 H Cl Cl Cl CF₃ H Cl O CH(CH₃) O CH₂CH₂F P1618 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂F P1619 H Cl Cl Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₂F P1620 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₃ P1621 H Cl Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₃ P1622 H Cl Cl Cl CF₃ H Cl O CH(CH₃) O CH₂CH₃ P1623 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₃ P1624 H Cl Cl Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₃ P1625 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH(CH₃)CF₃ P1626 H Cl Cl Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1627 H Cl Cl Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1628 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1629 H Cl Cl Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1630 H Cl Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₂CF₃ P1631 H Cl Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1632 H Cl Cl Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1633 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1634 H Cl Cl Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1635 H Cl Cl Cl CF₃ H H O CH(CH₂CH₃) O CH₂CF₃ P1636 H Cl Cl Cl CF₃ H H O C(CH₃)₂ O CH₂CF₃ P1637 H Cl Cl Cl CF₃ H H O CH₂CH₂ O CH₂CF₃ P1638 H Cl Cl Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1639 H Cl Cl Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1640 H Cl Cl Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1641 H Cl Cl Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1642 H Cl H Cl CF₃ H H O CH₂ O CH₂CF₃ P1643 H Cl H Cl CF₃ H Br O CH₂ O CH₂CF₃ P1644 H Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P1645 H Cl H Cl CF₃ H H O CH₂ S CH₂CF₃ P1646 H Cl H Cl CF₃ H Br O CH₂ S CH₂CF₃ P1647 H Cl H Cl CF₃ H Cl O CH₂ S CH₂CF₃ P1648 H Cl H Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P1649 H Cl H Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P1650 H Cl H Cl CF₃ H H S CH₂ O CH₂CF₃ P1651 H Cl H Cl CF₃ H Br S CH₂ O CH₂CF₃ P1652 H Cl H Cl CF₃ H Cl S CH₂ O CH₂CF₃ P1653 H Cl H Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P1654 H Cl H Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P1655 H Cl H Cl CF₃ H H O CH₂ O CH₂CHF₂ P1656 H Cl H Cl CF₃ H Br O CH₂ O CH₂CHF₂ P1657 H Cl H Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P1658 H Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1659 H Cl H Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1660 H Cl H Cl CF₃ H H O CH₂ O CH₂CH₂F P1661 H Cl H Cl CF₃ H Br O CH₂ O CH₂CH₂F P1662 H Cl H Cl CF₃ H Cl O CH₂ O CH₂CH₂F P1663 H Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CH₂F P1664 H Cl H Cl CF₃ H CH₃ O CH₂ O CH₂CH₂F P1665 H Cl H Cl CF₃ H H O CH₂ O CH₂CH₃ P1666 H Cl H Cl CF₃ H Br O CH₂ O CH₂CH₃ P1667 H Cl H Cl CF₃ H Cl O CH₂ O CH₂CH₃ P1668 H Cl H Cl CF₃ H CF₃ O CH₂ O CH₂CH₃ P1669 H Cl H Cl CF₃ H CH₃ O CH₂ O CH₂CH₃ P1670 H Cl H Cl CF₃ CF₃ H O CH₂ O CH₂CF₃ P1671 H Cl H Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1672 H Cl H Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1673 H Cl H Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1674 H Cl H Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1675 H Cl H Cl CF₂CF₃ H H O CH₂ O CH₂CF₃ P1676 H Cl H Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1677 H Cl H Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1678 H Cl H Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1679 H Cl H Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1680 H Cl H Cl CF₃ H H O CH₂ O CH(CH₃)CF₃ P1681 H Cl H Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1682 H Cl H Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1683 H Cl H Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1684 H Cl H Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1685 H Cl H Cl CF₃ CF₃ H O CH(CH₃) O CH₂CF₃ P1686 H Cl H Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1687 H Cl H Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1688 H Cl H Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1689 H Cl H Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1690 H Cl H Cl CF₂CF₃ H H O CH (CH₃) O CH₂CF₃ P1691 H Cl H Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1692 H Cl H Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1693 H Cl H Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1694 H Cl H Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1695 H Cl H Cl CF₃ H H O CH(CH₃) O CH₂CF₃ P1696 H Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P1697 H Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1698 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1699 H Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1700 H Cl H Cl CF₃ H H O CH(CH₃) S CH₂CF₃ P1701 H Cl H Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P1702 H Cl H Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1703 H Cl H Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1704 H Cl H Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1705 H Cl H Cl CF₃ H H S CH(CH₃) O CH₂CF₃ P1706 H Cl H Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P1707 H Cl H Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1708 H Cl H Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1709 H Cl H Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1710 H Cl H Cl CF₃ H H O CH(CH₃) O CH₂CHF₂ P1711 H Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1712 H Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1713 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1714 H Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1715 H Cl H Cl CF₃ H H O CH(CH₃) O CH₂CH₂F P1716 H Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CH₂F P1717 H Cl H Cl CF₃ H Cl O CH(CH₃) O CH₂CH₂F P1718 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂F P1719 H Cl H Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₂F P1720 H Cl H Cl CF₃ H H O CH(CH₃) O CH₂CH₃ P1721 H Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CH₃ P1722 H Cl H Cl CF₃ H Cl O CH(CH₃) O CH₂CH₃ P1723 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₃ P1724 H Cl H Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₃ P1725 H Cl H Cl CF₃ H H O CH(CH₃) O CH(CH₃)CF₃ P1726 H Cl H Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1727 H Cl H Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1728 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1729 H Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1730 H Cl H Cl CF₃ H H O CH(CH₃) O CH₂CH₂CF₃ P1731 H Cl H Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1732 H Cl H Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1733 H Cl H Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1734 H Cl H Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1735 H Cl H Cl CF₃ H H O CH(CH₂CH₃) O CH₂CF₃ P1736 H Cl H Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1737 H Cl H Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1738 H Cl H Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1739 H Cl H Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1740 H Cl H Cl CF₃ H H O C(CH₃)₂ O CH₂CF₃ P1741 H Cl H Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1742 H Cl H Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1743 H Cl H Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1744 H Cl H Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1745 H Cl H Cl CF₃ H H O CH₂CH₂ O CH₂CF₃ P1746 H Cl H Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1747 H Cl H Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1748 H Cl H Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1749 H Cl H Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1750 H H Cl Cl CF₃ H H O CH₂ O CH₂CF₃ P1751 H H Cl Cl CF₃ H Br O CH₂ O CH₂CF₃ P1752 H H Cl Cl CF₃ H Cl O CH₂ O CH₂CF₃ P1753 H H Cl Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P1754 H H Cl Cl CF₃ H CH₃ O CH₂ O CH₂CF₃ P1755 H H Cl Cl CF₃ H H O CH₂ S CH₂CF₃ P1756 H H Cl Cl CF₃ H Br O CH₂ S CH₂CF₃ P1757 H H Cl Cl CF₃ H Cl O CH₂ S CH₂CF₃ P1758 H H Cl Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P1759 H H Cl Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P1760 H H Cl Cl CF₃ H H S CH₂ O CH₂CF₃ P1761 H H Cl Cl CF₃ H Br S CH₂ O CH₂CF₃ P1762 H H Cl Cl CF₃ H Cl S CH₂ O CH₂CF₃ P1763 H H Cl Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P1764 H H Cl Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P1765 H H Cl Cl CF₃ H H O CH₂ O CH₂CHF₂ P1766 H H Cl Cl CF₃ H Br O CH₂ O CH₂CHF₂ P1767 H H Cl Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P1768 H H Cl Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1769 H H Cl Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1770 H H Cl Cl CF₃ H H O CH₂ O CH₂CH₂F P1771 H H Cl Cl CF₃ H Br O CH₂ O CH₂CH₂F P1772 H H Cl Cl CF₃ H Cl O CH₂ O CH₂CH₂F P1773 H H Cl Cl CF₃ H CF₃ O CH₂ O CH₂CH₂F P1774 H H Cl Cl CF₃ H CH₃ O CH₂ O CH₂CH₂F P1775 H H Cl Cl CF₃ H H O CH₂ O CH₂CH₃ P1776 H H Cl Cl CF₃ H Br O CH₂ O CH₂CH₃ P1777 H H Cl Cl CF₃ H Cl O CH₂ O CH₂CH₃ P1778 H H Cl Cl CF₃ H CF₃ O CH₂ O CH₂CH₃ P1779 H H Cl Cl CF₃ H CH₃ O CH₂ O CH₂CH₃ P1780 H H Cl Cl CF₃ CF₃ H O CH₂ O CH₂CF₃ P1781 H H Cl Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1782 H H Cl Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1783 H H Cl Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1784 H H Cl Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1785 H H Cl Cl CF₂CF₃ H H O CH₂ O CH₂CF₃ P1786 H H Cl Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1787 H H Cl Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1788 H H Cl Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1789 H H Cl Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1790 H H Cl Cl CF₃ H H O CH₂ O CH(CH₃)CF₃ P1791 H H Cl Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1792 H H Cl Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1793 H H Cl Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1794 H H Cl Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1795 H H Cl Cl CF₃ CF₃ H O CH(CH₃) O CH₂CF₃ P1796 H H Cl Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1797 H H Cl Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1798 H H Cl Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1799 H H Cl Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1800 H H Cl Cl CF₂CF₃ H H O CH (CH₃) O CH₂CF₃ P1801 H H Cl Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1802 H H Cl Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1803 H H Cl Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1804 H H Cl Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1805 H H Cl Cl CF₃ H H O CH(CH₃) O CH₂CF₃ P1806 H H Cl Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P1807 H H Cl Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1808 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1809 H H Cl Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1810 H H Cl Cl CF₃ H H O CH(CH₃) S CH₂CF₃ P1811 H H Cl Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P1812 H H Cl Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1813 H H Cl Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1814 H H Cl Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1815 H H Cl Cl CF₃ H H S CH(CH₃) O CH₂CF₃ P1816 H H Cl Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P1817 H H Cl Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1818 H H Cl Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1819 H H Cl Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1820 H H Cl Cl CF₃ H H O CH(CH₃) O CH₂CHF₂ P1821 H H Cl Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1822 H H Cl Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1823 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1824 H H Cl Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1825 H H Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₂F P1826 H H Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₂F P1827 H H Cl Cl CF₃ H Cl O CH(CH₃) O CH₂CH₂F P1828 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂F P1829 H H Cl Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₂F P1830 H H Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₃ P1831 H H Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₃ P1832 H H Cl Cl CF₃ H Cl O CH(CH₃) O CH₂CH₃ P1833 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₃ P1834 H H Cl Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₃ P1835 H H Cl Cl CF₃ H H O CH(CH₃) O CH(CH₃)CF₃ P1836 H H Cl Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1837 H H Cl Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1838 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1839 H H Cl Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1840 H H Cl Cl CF₃ H H O CH(CH₃) O CH₂CH₂CF₃ P1841 H H Cl Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1842 H H Cl Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1843 H H Cl Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1844 H H Cl Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1845 H H Cl Cl CF₃ H H O CH(CH₂CH₃) O CH₂CF₃ P1846 H H Cl Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1847 H H Cl Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1848 H H Cl Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1849 H H Cl Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1850 H H Cl Cl CF₃ H H O C(CH₃)₂ O CH₂CF₃ P1851 H H Cl Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1852 H H Cl Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1853 H H Cl Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1854 H H Cl Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1855 H H Cl Cl CF₃ H H O CH₂CH₂ O CH₂CF₃ P1856 H H Cl Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1857 H H Cl Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1858 H H Cl Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1859 H H Cl Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1860 H Cl F Cl CF₃ H H O CH₂ O CH₂CF₃ P1861 H Cl F Cl CF₃ H Cl O CH₂ O CH₂CF₃ P1862 H Cl F Cl CF₃ H CF₃ O CH₂ O CH₂CF₃ P1863 H Cl F Cl CF₃ H H O CH₂ S CH₂CF₃ P1864 H Cl F Cl CF₃ H Br O CH₂ S CH₂CF₃ P1865 H Cl F Cl CF₃ H Cl O CH₂ S CH₂CF₃ P1866 H Cl F Cl CF₃ H CF₃ O CH₂ S CH₂CF₃ P1867 H Cl F Cl CF₃ H CH₃ O CH₂ S CH₂CF₃ P1868 H Cl F Cl CF₃ H H S CH₂ O CH₂CF₃ P1869 H Cl F Cl CF₃ H Br S CH₂ O CH₂CF₃ P1870 H Cl F Cl CF₃ H Cl S CH₂ O CH₂CF₃ P1871 H Cl F Cl CF₃ H CF₃ S CH₂ O CH₂CF₃ P1872 H Cl F Cl CF₃ H CH₃ S CH₂ O CH₂CF₃ P1873 H Cl F Cl CF₃ H H O CH₂ O CH₂CHF₂ P1874 H Cl F Cl CF₃ H Br O CH₂ O CH₂CHF₂ P1875 H Cl F Cl CF₃ H Cl O CH₂ O CH₂CHF₂ P1876 H Cl F Cl CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1877 H Cl F Cl CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1878 H Cl F Cl CF₃ H H O CH₂ O CH₂CH₂F P1879 H Cl F Cl CF₃ H Br O CH₂ O CH₂CH₂F P1880 H Cl F Cl CF₃ H Cl O CH₂ O CH₂CH₂F P1881 H Cl F Cl CF₃ H CF₃ O CH₂ O CH₂CH₂F P1882 H Cl F Cl CF₃ H CH₃ O CH₂ O CH₂CH₂F P1883 H Cl F Cl CF₃ H H O CH₂ O CH₂CH₃ P1884 H Cl F Cl CF₃ H Br O CH₂ O CH₂CH₃ P1885 H Cl F Cl CF₃ H Cl O CH₂ O CH₂CH₃ P1886 H Cl F Cl CF₃ H CF₃ O CH₂ O CH₂CH₃ P1887 H Cl F Cl CF₃ H CH₃ O CH₂ O CH₂CH₃ P1888 H Cl F Cl CF₃ CF₃ H O CH₂ O CH₂CF₃ P1889 H Cl F Cl CF₃ CF₃ Br O CH₂ O CH₂CF₃ P1890 H Cl F Cl CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P1891 H Cl F Cl CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P1892 H Cl F Cl CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P1893 H Cl F Cl CF₂CF₃ H H O CH₂ O CH₂CF₃ P1894 H Cl F Cl CF₂CF₃ H Br O CH₂ O CH₂CF₃ P1895 H Cl F Cl CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P1896 H Cl F Cl CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P1897 H Cl F Cl CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P1898 H Cl F Cl CF₃ H H O CH₂ O CH(CH₃)CF₃ P1899 H Cl F Cl CF₃ H Br O CH₂ O CH(CH₃)CF₃ P1900 H Cl F Cl CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P1901 H Cl F Cl CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P1902 H Cl F Cl CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P1903 H Cl F Cl CF₃ CF₃ H O CH(CH₃) O CH₂CF₃ P1904 H Cl F Cl CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P1905 H Cl F Cl CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P1906 H Cl F Cl CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P1907 H Cl F Cl CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P1908 H Cl F Cl CF₂CF₃ H H O CH (CH₃) O CH₂CF₃ P1909 H Cl F Cl CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P1910 H Cl F Cl CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1911 H Cl F Cl CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P1912 H Cl F Cl CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1913 H Cl F Cl CF₃ H H O CH(CH₃) O CH₂CF₃ P1914 H Cl F Cl CF₃ H Br O CH(CH₃) O CH₂CF₃ P1915 H Cl F Cl CF₃ H Cl O CH (CH₃) O CH₂CF₃ P1916 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CF₃ P1917 H Cl F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P1918 H Cl F Cl CF₃ H H O CH(CH₃) S CH₂CF₃ P1919 H Cl F Cl CF₃ H Br O CH(CH₃) S CH₂CF₃ P1920 H Cl F Cl CF₃ H Cl O CH (CH₃) S CH₂CF₃ P1921 H Cl F Cl CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P1922 H Cl F Cl CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P1923 H Cl F Cl CF₃ H H S CH(CH₃) O CH₂CF₃ P1924 H Cl F Cl CF₃ H Br S CH(CH₃) O CH₂CF₃ P1925 H Cl F Cl CF₃ H Cl S CH (CH₃) O CH₂CF₃ P1926 H Cl F Cl CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P1927 H Cl F Cl CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P1928 H Cl F Cl CF₃ H H O CH(CH₃) O CH₂CHF₂ P1929 H Cl F Cl CF₃ H Br O CH(CH₃) O CH₂CHF₂ P1930 H Cl F Cl CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P1931 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P1932 H Cl F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P1933 H Cl F Cl CF₃ H H O CH(CH₃) O CH₂CH₂F P1934 H Cl F Cl CF₃ H Br O CH(CH₃) O CH₂CH₂F P1935 H Cl F Cl CF₃ H Cl O CH(CH₃) O CH₂CH₂F P1936 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂F P1937 H Cl F Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₂F P1938 H Cl F Cl CF₃ H H O CH(CH₃) O CH₂CH₃ P1939 H Cl F Cl CF₃ H Br O CH(CH₃) O CH₂CH₃ P1940 H Cl F Cl CF₃ H Cl O CH(CH₃) O CH₂CH₃ P1941 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₃ P1942 H Cl F Cl CF₃ H CH₃ O CH(CH₃) O CH₂CH₃ P1943 H Cl F Cl CF₃ H H O CH(CH₃) O CH(CH₃)CF₃ P1944 H Cl F Cl CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P1945 H Cl F Cl CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P1946 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P1947 H Cl F Cl CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P1948 H Cl F Cl CF₃ H H O CH(CH₃) O CH₂CH₂CF₃ P1949 H Cl F Cl CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P1950 H Cl F Cl CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P1951 H Cl F Cl CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P1952 H Cl F Cl CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P1953 H Cl F Cl CF₃ H H O CH(CH₂CH₃) O CH₂CF₃ P1954 H Cl F Cl CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P1955 H Cl F Cl CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P1956 H Cl F Cl CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P1957 H Cl F Cl CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P1958 H Cl F Cl CF₃ H H O C(CH₃)₂ O CH₂CF₃ P1959 H Cl F Cl CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P1960 H Cl F Cl CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P1961 H Cl F Cl CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P1962 H Cl F Cl CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P1963 H Cl F Cl CF₃ H H O CH₂CH₂ O CH₂CF₃ P1964 H Cl F Cl CF₃ H Br O CH₂CH₂ O CH₂CF₃ P1965 H Cl F Cl CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P1966 H Cl F Cl CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P1967 H Cl F Cl CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃ P1968 H Br H Br CF₃ H H O CH₂ O CH₂CF₃ P1969 H Br H Br CF₃ H Br O CH₂ O CH₂CF₃ P1970 H Br H Br CF₃ H Cl O CH₂ O CH₂CF₃ P1971 H Br H Br CF₃ H CF₃ O CH₂ O CH₂CF₃ P1972 H Br H Br CF₃ H CH₃ O CH₂ O CH₂CF₃ P1973 H Br H Br CF₃ H H O CH₂ S CH₂CF₃ P1974 H Br H Br CF₃ H Br O CH₂ S CH₂CF₃ P1975 H Br H Br CF₃ H Cl O CH₂ S CH₂CF₃ P1976 H Br H Br CF₃ H CF₃ O CH₂ S CH₂CF₃ P1977 H Br H Br CF₃ H CH₃ O CH₂ S CH₂CF₃ P1978 H Br H Br CF₃ H H S CH₂ O CH₂CF₃ P1979 H Br H Br CF₃ H Br S CH₂ O CH₂CF₃ P1980 H Br H Br CF₃ H Cl S CH₂ O CH₂CF₃ P1981 H Br H Br CF₃ H CF₃ S CH₂ O CH₂CF₃ P1982 H Br H Br CF₃ H CH₃ S CH₂ O CH₂CF₃ P1983 H Br H Br CF₃ H H O CH₂ O CH₂CHF₂ P1984 H Br H Br CF₃ H Br O CH₂ O CH₂CHF₂ P1985 H Br H Br CF₃ H Cl O CH₂ O CH₂CHF₂ P1986 H Br H Br CF₃ H CF₃ O CH₂ O CH₂CHF₂ P1987 H Br H Br CF₃ H CH₃ O CH₂ O CH₂CHF₂ P1988 H Br H Br CF₃ H H O CH₂ O CH₂CH₂F P1989 H Br H Br CF₃ H Br O CH₂ O CH₂CH₂F P1990 H Br H Br CF₃ H Cl O CH₂ O CH₂CH₂F P1991 H Br H Br CF₃ H CF₃ O CH₂ O CH₂CH₂F P1992 H Br H Br CF₃ H CH₃ O CH₂ O CH₂CH₂F P1993 H Br H Br CF₃ H H O CH₂ O CH₂CH₃ P1994 H Br H Br CF₃ H Br O CH₂ O CH₂CH₃ P1995 H Br H Br CF₃ H Cl O CH₂ O CH₂CH₃ P1996 H Br H Br CF₃ H CF₃ O CH₂ O CH₂CH₃ P1997 H Br H Br CF₃ H CH₃ O CH₂ O CH₂CH₃ P1998 H Br H Br CF₃ CF₃ H O CH₂ O CH₂CF₃ P1999 H Br H Br CF₃ CF₃ Br O CH₂ O CH₂CF₃ P2000 H Br H Br CF₃ CF₃ Cl O CH₂ O CH₂CF₃ P2001 H Br H Br CF₃ CF₃ CF₃ O CH₂ O CH₂CF₃ P2002 H Br H Br CF₃ CF₃ CH₃ O CH₂ O CH₂CF₃ P2003 H Br H Br CF₂CF₃ H H O CH₂ O CH₂CF₃ P2004 H Br H Br CF₂CF₃ H Br O CH₂ O CH₂CF₃ P2005 H Br H Br CF₂CF₃ H Cl O CH₂ O CH₂CF₃ P2006 H Br H Br CF₂CF₃ H CF₃ O CH₂ O CH₂CF₃ P2007 H Br H Br CF₂CF₃ H CH₃ O CH₂ O CH₂CF₃ P2008 H Br H Br CF₃ H H O CH₂ O CH(CH₃)CF₃ P2009 H Br H Br CF₃ H Br O CH₂ O CH(CH₃)CF₃ P2010 H Br H Br CF₃ H Cl O CH₂ O CH(CH₃)CF₃ P2011 H Br H Br CF₃ H CF₃ O CH₂ O CH(CH₃)CF₃ P2012 H Br H Br CF₃ H CH₃ O CH₂ O CH(CH₃)CF₃ P2013 H Br H Br CF₃ CF₃ H O CH(CH₃) O CH₂CF₃ P2014 H Br H Br CF₃ CF₃ Br O CH(CH₃) O CH₂CF₃ P2015 H Br H Br CF₃ CF₃ Cl O CH (CH₃) O CH₂CF₃ P2016 H Br H Br CF₃ CF₃ CF₃ O CH(CH₃) O CH₂CF₃ P2017 H Br H Br CF₃ CF₃ CH₃ O CH (CH₃) O CH₂CF₃ P2018 H Br H Br CF₂CF₃ H H O CH (CH₃) O CH₂CF₃ P2019 H Br H Br CF₂CF₃ H Br O CH (CH₃) O CH₂CF₃ P2020 H Br H Br CF₂CF₃ H Cl O CH (CH₃) O CH₂CF₃ P2021 H Br H Br CF₂CF₃ H CF₃ O CH (CH₃) O CH₂CF₃ P2022 H Br H Br CF₂CF₃ H CH₃ O CH (CH₃) O CH₂CF₃ P2023 H Br H Br CF₃ H H O CH(CH₃) O CH₂CF₃ P2024 H Br H Br CF₃ H Cl O CH (CH₃) O CH₂CF₃ P2025 H Br H Br CF₃ H H O CH(CH₃) S CH₂CF₃ P2026 H Br H Br CF₃ H Br O CH(CH₃) S CH₂CF₃ P2027 H Br H Br CF₃ H Cl O CH (CH₃) S CH₂CF₃ P2028 H Br H Br CF₃ H CF₃ O CH(CH₃) S CH₂CF₃ P2029 H Br H Br CF₃ H CH₃ O CH (CH₃) S CH₂CF₃ P2030 H Br H Br CF₃ H H S CH(CH₃) O CH₂CF₃ P2031 H Br H Br CF₃ H Br S CH(CH₃) O CH₂CF₃ P2032 H Br H Br CF₃ H Cl S CH (CH₃) O CH₂CF₃ P2033 H Br H Br CF₃ H CF₃ S CH(CH₃) O CH₂CF₃ P2034 H Br H Br CF₃ H CH₃ S CH (CH₃) O CH₂CF₃ P2035 H Br H Br CF₃ H H O CH(CH₃) O CH₂CHF₂ P2036 H Br H Br CF₃ H Br O CH(CH₃) O CH₂CHF₂ P2037 H Br H Br CF₃ H Cl O CH (CH₃) O CH₂CHF₂ P2038 H Br H Br CF₃ H CF₃ O CH(CH₃) O CH₂CHF₂ P2039 H Br H Br CF₃ H CH₃ O CH (CH₃) O CH₂CHF₂ P2040 H Br H Br CF₃ H H O CH(CH₃) O CH₂CH₂F P2041 H Br H Br CF₃ H Br O CH(CH₃) O CH₂CH₂F P2042 H Br H Br CF₃ H Cl O CH(CH₃) O CH₂CH₂F P2043 H Br H Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₂F P2044 H Br H Br CF₃ H CH₃ O CH(CH₃) O CH₂CH₂F P2045 H Br H Br CF₃ H H O CH(CH₃) O CH₂CH₃ P2046 H Br H Br CF₃ H Br O CH(CH₃) O CH₂CH₃ P2047 H Br H Br CF₃ H Cl O CH(CH₃) O CH₂CH₃ P2048 H Br H Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₃ P2049 H Br H Br CF₃ H CH₃ O CH(CH₃) O CH₂CH₃ P2050 H Br H Br CF₃ H H O CH(CH₃) O CH(CH₃)CF₃ P2051 H Br H Br CF₃ H Br O CH(CH₃) O CH(CH₃)CF₃ P2052 H Br H Br CF₃ H Cl O CH (CH₃) O CH(CH₃)CF₃ P2053 H Br H Br CF₃ H CF₃ O CH(CH₃) O CH(CH₃)CF₃ P2054 H Br H Br CF₃ H CH₃ O CH (CH₃) O CH(CH₃)CF₃ P2055 H Br H Br CF₃ H H O CH(CH₃) O CH₂CH₂CF₃ P2056 H Br H Br CF₃ H Br O CH(CH₃) O CH₂CH₂CF₃ P2057 H Br H Br CF₃ H Cl O CH (CH₃) O CH₂CH₂CF₃ P2058 H Br H Br CF₃ H CF₃ O CH(CH₃) O CH₂CH₂CF₃ P2059 H Br H Br CF₃ H CH₃ O CH (CH₃) O CH₂CH₂CF₃ P2060 H Br H Br CF₃ H H O CH(CH₂CH₃) O CH₂CF₃ P2061 H Br H Br CF₃ H Br O CH(CH₂CH₃) O CH₂CF₃ P2062 H Br H Br CF₃ H Cl O CH(CH₂CH₃) O CH₂CF₃ P2063 H Br H Br CF₃ H CF₃ O CH(CH₂CH₃) O CH₂CF₃ P2064 H Br H Br CF₃ H CH₃ O CH(CH₂CH₃) O CH₂CF₃ P2065 H Br H Br CF₃ H H O C(CH₃)₂ O CH₂CF₃ P2066 H Br H Br CF₃ H Br O C(CH₃)₂ O CH₂CF₃ P2067 H Br H Br CF₃ H Cl O C(CH₃)₂ O CH₂CF₃ P2068 H Br H Br CF₃ H CF₃ O C(CH₃)₂ O CH₂CF₃ P2069 H Br H Br CF₃ H CH₃ O C(CH₃)₂ O CH₂CF₃ P2070 H Br H Br CF₃ H H O CH₂CH₂ O CH₂CF₃ P2071 H Br H Br CF₃ H Br O CH₂CH₂ O CH₂CF₃ P2072 H Br H Br CF₃ H Cl O CH₂CH₂ O CH₂CF₃ P2073 H Br H Br CF₃ H CF₃ O CH₂CH₂ O CH₂CF₃ P2074 H Br H Br CF₃ H CH₃ O CH₂CH₂ O CH₂CF₃

Example A Bioassays on Beet Armyworm (“Baw”) and Corn Earworm (“CEW”) and Cabbage Looper (“CL”)

BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be resistant to certain insecticides. CL is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.

Certain molecules disclosed in this document were tested against BAW, CEW and CL using procedures described in the following examples. In the reporting of the results, the “BAW & CEW & CL Rating Table” was used (See Table Section).

Bioassays on BAW (spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the tables entitled “Table 3: Assay Results Part 1” and “Table 4: Assay Results Part 2” (See Table Section).

Bioassays on CEW (Helicoverpa zea)

Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 3: Assay Results Part 1” (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One to five second instar CL larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 4: Assay Results Part 2” (See Table Section).

Example B Bioassays on green peach aphid (“GPA”) (Myzus persicae)

GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the “GPA Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/MeOH (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5× with 0.025% Tween 20 in water to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/MeOH (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25° C. and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W. S. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp. 265-267) as follows.

Corrected % Control=100*(X−Y)/X

-   -   where     -   X=No. of live aphids on solvent check plants and     -   Y=No. of live aphids on treated plants

The results are indicated in the tables entitled “Table 3: Assay Results Part 1” and “Table 4: Assay Results Part 2” (See Table Section).

Pesticidally Acceptable Acid Addition Salts, Salt Derivatives, Solvates, Ester Derivatives, Polymorphs, Isotopes and Radionuclides

Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By way of a non-limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous NaOH, potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as “solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent.

Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having ²H (also known as deuterium) in place of ¹H.

Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.

Combinations

Molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists. Examples of such compounds in the above groups that may be used with the Molecules of Formula One are—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-5-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlomidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DB CP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl, fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluoron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluoron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid. For more information consult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located at http://www.alanwood.net/pesticides/index.html. Also consult “THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.

Biopesticides

Molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The term “biopesticide” is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinemema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In one embodiment, the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more of the following:

-   1.     3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; -   2.     3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; -   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; -   4.     4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; -   5.     3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide; -   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; -   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; -   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; -   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; -   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; -   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; -   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; -   13.     3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide; -   14.     N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone; -   15.     N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone     nicotine; -   16.     0-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methyl     thiocarbonate; -   17.     (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine; -   18.     1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol; -   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl     mesylate; and -   20.     N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.

Synergistic Mixtures

Molecules of Formula One may be used with certain active compounds to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the molecules of Formula One are the same, similar, or different. Examples of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Generally, weight ratios of the molecules of Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and in another embodiment about 1:1.

Formulations

A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra-low volume solutions. For further information on formulation types see “Catalogue of Pesticide Formulation Types and International Coding System” Technical Monograph n° 2, 5th Edition by CropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.

It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest's respiratory system or being absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.

Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non-ionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published Feb. 1, 2007, having patent application Ser. No. 11/495,228. For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult “Handbook of Pest Control—The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic ‘backbones’ and a large number of ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.

An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil-in-water emulsions, suspoemulsions, and ultra-low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets. Thickening, gelling, and anti-settling agents generally fall into two categories, namely water-insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.

For further information, see “Chemistry and Technology of Agrochemical Formulations” edited by D. A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see “Insecticides in Agriculture and Environment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fiiscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fiisca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THE BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula One are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can come about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.

The molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low.

The molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.

Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molecules of Formula One may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.

Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as “Roundup Ready” seed, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits. Furthermore, such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.

Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecules of Formula One may also be used on such new invasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.

A molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not be used to interpret any portion hereof.

TABLE SECTION

% Control (or Mortality) Rating BAW, CEW & CL Rating Table 50-100 A More than 0-Less than 50 B Not Tested C No activity noticed in this bioassay D GPA Rating Table 80-100 A More than 0-Less than 80 B Not Tested C No activity noticed in this bioassay D

TABLE 1 Structures for Compounds Compound Number Structure AI34

AI36

AI37

AI38

AI39

AI40

AI41

AI44

AI45

AC1

AC2

AC3

AC4

AC5

AC6

AC7

AC8

AC9

AC10

AC11

AC12

AC13

AC14

AC15

AC16

AC17

AC18

AC19

AC20

AC21

AC22

AC23

AC24

AC25

AC26

AC27

AC28

AC29

AC30

AC31

AC32

AC33

AC34

AC35

AC36

AC37

AC38

AC39

AC40

AC41

AC42

AC43

AC44

AC45

AC46

AC47

AC48

AC49

AC50

AC51

AC52

AC53

AC54

AC57

AC58

AC59

AC60

AC61

AC62

AC63

AC64

AC65

AC66

AC67

AC68

AC69

AC70

AC71

AC72

AC75

AC76

AC77

AC78

AC79

AC80

AC81

AC82

AC83

AC84

AC85

AC86

AC87

AC89

AC90

AC91

AC92

AC93

AC94

AC95

AC96

AC97

AC98

AC99

AC100

AC101

AC102

AC103

AC104

AC105

AC106

AC107

AC108

AC109

AC110

AC111

AC112

AC113

AC114

AC115

AC116

AC117

AC118

BC1

BC2

BC3

BC4

BC5

BC6

BC7

BC8

BC9

BC10

BC11

BC12

BC13

BC14

CI4

CI5

CI8

CI9

CI34

CI35

CI36

CI37

CI38

CI39

CI40

CI41

CI49

CI50

CI51

CI52

CI53

CI54

CI55

CI56

CI57

CC1

CC2

CC3

CC4

CC5

CC6

CC7

CC8

CC9

CC10

CC11

CC12

CC13

CC14

CC15

CC16

CC17

CC18

CC19

CC20

CC21

CC22

CC23

CC24

CC25

CC26

CC27

CC28

CC29

CC30

CC31

CC32

CC33

CC34

CC35

CC36

CC37

CC38

CC39

CC40

CC41

CC42

CC43

CC44

CC45

CC46

CC47

CC48

CC49

CC50

CC51

CC52

CC53

CC54

DC1

DC2

DC3

DC4

DC5

DC6

DC7

DC8

DC9

DC10

DC11

DC12

DC13

DC14

DC15

DC16

DC17

DC18

DC19

DC20

DC21

DC22

DC23

DC24

DC25

DC26

DC27

DC28

DC29

DC30

DC31

DC32

DC33

DC34

DC35

DC36

DC37

DC38

DC39

DC40

DC41

DC42

DC43

DC44

DC45

DC46

DC47

DC48

DC49

DC50

DC51

DC52

DC53

DC54

DC55

DC56

DC57

DC58

DC59

DC60

DC61

DC62

DC63

DC64

DC65

DC66

DC67

DC68

DC69

DC70

TABLE 1A Structures for F Compounds Compound Prepared as Number Structure Appearance in Example: F1

white foam 135 F2

brown gum 15 F3

pale yellow gum 15 F4

yellow solid 15 F5

108 F6

108 F7

yellow solid 15 F8

off-white solid 15 F8A

pale yellow solid 15 F9

yellow solid 15 F10

off-white solid 132 F11

off-white solid 132 F12

off-white solid 133 F13

off-white solid 133 F14

pale yellow solid 15 F15

yellow solid 15 F15A

yellow solid 15 F16

pale yellow solid 15 F16A

yellow solid 15 F17

off-white solid 15 F18

yellow solid 15 F19

yellow gum 15 F20

yellow solid 15 F20A

off-white solid 133 F20B

off-white solid 133 F20C

white solid 88 F21

yellow gum 15 F22

light brown gum 15 F23

pale yellow liquid 15 F23A

yellow solid 15 F24

pale yellow liquid 15 F25

yellow solid 15 F26

brown gum 15 F27

pale yellow gum 15 F28

brown gum 15 F29

pale yellow gum 19 F30

brown gum 15 F31

pale yellow gum 134

TABLE 1B Structures of Prophetic Compounds Subsequently Exemplified Compound Prepared as Number Structure Appearance in Example: P1

Yellow solid 15 P2

Brown gum 15 P12

Off white solid 15 P14

Light yellow gum 19 P15

Light yellow gum 19 P82

Brown semi solid 15 P84

Pale yellow solid 15 P156

Green liquid 15 P226

Brown semi solid 15 P228

Brown semi solid 15 P298

Yellow solid 15 P300

Brown gum 15 P442

Pale yellow solid 15 P444

Pale yellow solid 15 P514

Off white solid 15 P516

Brown solid 15 P568

Brown semi solid 15 P586

Brown semi solid 15 P588

Brown semi solid 15 P660

Pale yellow solid 15 P730

Yellow solid 15 P732

Brown semi solid 15 P802

Brown gum 15 P804

Brown gum 15 P1090

Light brown solid 15 P1092

Brown semi solid 15 P1197

Off white solid 15 P1269

Pale yellow solid 15 P1340

Pale yellow liquid 15 P1411

Pale yellow liquid 15 P1483

Off white solid 15 P1556

Brown solid 15 P1558

Brown solid 134 P1559

Brown gum 134 P1560

Off white solid 19 P1564

Yellow solid 19 P1566

Brown solid 15 P1589

Pale yellow gum 15 P1591

Brown gum 15 P1592

Pale yellow gum 15 P1599

Brown semi solid 12 P1601

Brown viscous liquid 15 P1603

Off white solid 135 P1611A

Pale yellow solid 137 P1613A

Brown solid 137 P1616

Brown gum 15 P1616A

Pale yellow semi solid 137 P1618A

Brown solid 137 P1621

Brown viscous liquid 12 P1623

Brown liquid 12 P1624

Brown semi solid 12 P1631A

Brown viscous liquid 137 P1633A

Brown solid 137 P1636

Off white solid 135 P1638

Pale yellow solid 15 P1640

Brown semi solid 15 P1641

Brown solid 15 P1691

Brown gum 15 P1693

Pale yellow semi solid 15 P1696

Yellow solid 15 P1698

Yellow semi solid 15 P1776

White solid 15 P1781

White solid 15 P1806

Brown gum 15 P1808

Pale yellow gum 15 P1862

Off white gum 15 P1864

Brown gum 19 P1866

Brown liquid 19 P1969

Brown solid 15 P1970

Brown gum 15 P1971

Pale yellow solid 15 P1972

Light brown solid 15 P2009

Yellow solid 15 P2010

Yellow gum 15 P2011

Yellow solid 15 P2012

Off white solid 15 P2036

Brown solid 15 P2038

Yellow liquid 15 P2041

Brown solid 15 P2043

Dark green solid 15 P2056

Brown solid 15 P2058

Pale yellow semi solid 15

TABLE 1C Structures for FA Compounds Prepared as Compound in Number Structure Appearance Example: FA1

Pale yellow gum 15 FA2

Light green liquid 15 FA3

Brown gum 15 FA4

White foam 138 FA5

White foam 138 FA6

Yellow solid 146 FA7

Pale yellow solid 137 FA8

Pale yellow gum 15 FA9

Yellow gum 134 FA10

Yellow gum 134 FA11

Brown semi solid 134 FA12

Brown semi solid 134 FA13

Light green solid 147 FA14

White foam 142 FA15

White foam 142 FA16

Pale yellow solid 15 FA17

Off white solid 15 FA18

Yellow semi solid 15 FA19

Pale yellow solid 15 FA20

Pale yellow solid 15 FA21

Brown gum 15 FA22

Yellow gum 15 FA23

Light yellow oil 142 FA24

Off white solid 15 FA25

Yellow solid 15 FA26

Light green solid 12 FA27

Pale green solid 12 FA28

Brown solid 15 FA29

Brown liquid 15 FA30

Brown gum 12 FA31

Pale yellow solid 12 FA32

Yellow solid 15 FA33

Yellow solid 135 FA34

Off white solid 149

TABLE 2 Analytical Data for Compounds in Table 1. Compound mp Number (° C.) ESIMS ¹H NMR (δ)^(a) IR (cm⁻¹) AC1 156-161 386.09 ([M − H]⁻) 7.83 (m, 2H), 7.68-7.63 (m, 5H), 6.93 (dd, J = 15.6, 8.0 Hz, 1H), 6.81 (d J = 15.6 Hz, 1H,), 4.15 (m, 1H), 2.80 (s, 3H) AC2 110-112 374 ([M + H]⁺) 7.80 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.38 (m, 1H), 7.30 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) AC3 162-166 402.24 ([M + H]⁺) 7.42 (m, 4H), 7.37 (t, J = 1.8 Hz, 1H), 7.28 (s, 2H), 6.63 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H), 3.20 (s, 3H), 3.00 (s, 3H) AC4 122-126 454 ([M − H]⁻) 7.79 (d, J = 1.2 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.30 (s, 2H), 6.64 (d, J = 15.6 Hz, 1H), 6.40 (dd, J = 15.6, 8.0 Hz, 1H), 6.30 (m, 1H), 4.15 (m, 3H) AC5 444.12 ([M + H]⁺) 7.67 (s, 3H), 7.64 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 6.91 (dd, J = 15.6, 8.0 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.80 (m, 1H), 3.60 (br s, 8H) AC6 468.40 ([M − H]⁻) 7.40 (m, 2H), 7.26 (m, 1657, 1113, 3H), 6.56 (d, J = 16.0 Hz, 804 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H) AC7 511.02 ([M − H]⁻) 8.39 (s, 1H), 7.74 (m, 3276, 1645, 1H), 7.39 (m, 3H), 1111, 801 7.24 (m, 4H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (br s, 1H), 4.63 (m, 2H), 4.12 (m, 1H), 2.41 (s, 3H) AC8 454.11 ([M − H]⁻) 7.39 (s, 1H), 7.22 (m, 1748, 1112, 2H), 7.19 (m, 3H), 801 6.53 (d, J = 16.0 Hz, 1H), 6.39-6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H), 3.95 (t, J = 7.0 Hz, 2H), 2.62 (t, J = 8.0 Hz, 2H), 2.30 (s, 3H), 2.18 (m, 2H) AC9 494.02 ([M − H]⁻) 7.45 (t, J = 7.6 Hz, 1H), 3276, 1645, 7.36 (m, 2H), 7.21 (m, 1112, 801 3H), 7.15 (m, 4H), 6.56 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.4 Hz, 1H), 6.08 (br s, 1H), 4.68 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.44 (s, 3H) A10 140-143 458.00 ([M − H]⁻) 7.38 (t, J = 1.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.27 (m, 2H), 7.24 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (m 1H), 5.44 (m, 1H), 4.12 (m, 1H), 3.51 (m, 2H), 3.40 (m, 2H), 2.44 (s, 3H) AC11 476.17 ([M − H]⁻) 7.39-7.29 (m, 9H), 3287, 1644, 7.24 (m, 2H), 6.56 (d, J = 16.0 Hz, 1112, 801 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.99 (br s, 1H), 4.63 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H), 2.47 (s, 3H) AC12 479.30 ([M + H]⁺) 8.63 (d, J = 4.4 Hz, 1H), 3293, 1653, 7.71 (m, 1H), 7.47 (d, J = 8.4 Hz, 1112, 800 1H), 7.37 (m, 2H), 7.32 (m, 2H), 7.23 (m, 2H), 7.13 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.75 (d, J = 4.8 Hz, 2H), 4.12 (m, 1H), 2.49 (s, 3H) AC13 75-78 490.04 ([M − H]⁻) 7.38 (m, 2H), 7.27 (m, 3H), 7.23 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (m 1H), 6.42 (dd, J = 16.0, 8.4 Hz, 1H), 4.91 (m 1H), 4.64 (m, 2H), 4.14 (m, 1H), 4.04 (m, 2H), 2.46 (s, 3H) AC14 480.99 ([M + 2H]⁺) 8.63 (s, 2H), 7.76 (d, J = 8.0 Hz, 3293, 1645, 1H), 7.36 (m, 1113, 800 3H), 7.22 (m, 1H), 7.13 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.66 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC15 59-61 516.86 ([M − H]⁻) 7.45 (s, 1H), 7.37 (m, 3246, 1635, 1H), 7.34 (m, 1H), 1112, 801 7.26 (m, 3H), 7.22 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.71 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC16 506.93 ([M + H]⁺) 8.47 (m, 1H), 8.19 (s, 1657, 1113, 1H), 7.76 (m, 1H), 801 7.47 (m, 2H), 7.37 (m, 1H), 7.28 (m, 2H), 7.24 (m, 1H), 7.21 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.4 Hz, 1H), 4.12 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC17 70-73 494.98 ([M − H]⁻) 7.49 (m, 2H), 7.38 (m, 1H), 7.29 (m, 4H), 7.08 (m, 3H), 6.91 (m, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.48 (m, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.49 (s, 3H) AC18 155-158 480.44 ([M + H]⁺) 8.73 (d, J = 4.8 Hz, 2H), 7.53 (d, J = 8.4 Hz, 1H), 7.37 (m, 1H), 7.27 (m, 4H), 7.23 (m, 1H), 7.11 (m, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (d, J = 4.8 Hz, 2H), 4.13 (m, 1H), 2.52 (s, 3H) AC19 55-57 471.66 ([M + H]⁺) 7.37 (m, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.27 (m, 2H), 7.22 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (brs, 1H), 4.13 (m, 2H), 3.94 (m, 1H), 3.79 (m, 2H), 3.35 (m, 1H), 2.45 (s, 3H), 2.14 (m, 1H), 1.71 (m, 2H), 1.65 (m, 1H). AC20 467.68 ([M + H]⁺) 7.37 (m, 2H), 7.27 (m, 3437, 1664, 2H), 7.23 (m, 2H), 1265, 1114, 6.57 (d, J = 16.0 Hz, 1H), 746 6.38 (m, 3H), 6.01 (m, 1H), 4.63 (d, J = 5.6 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC21 61-64 528.78 ([M + H]⁺) 8.44 (s, 1H), 8.18 (s, 1H), 7.83 (br s, 1H), 7.38 (m, 2H), 7.27 (m, 2H), 7.25 (m, 2H), 7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.01 (s, 2H), 4.11 (m, 1H), 2.43 (s, 3H) AC22 545.08 ([M − H]⁻) 8.39 (s, 1H), 7.73 (m, 3270, 1642, 1H), 7.40 (s, 1H), 1111, 809 7.35 (m, 2H), 7.22 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (br s, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC23 492.35 ([M − H]⁻) 7.42 (s, 2H), 7.36 (m, 3273, 1641, 1H), 7.24 (m, 2H), 1250, 1113, 6.59 (d, J = 16.0 Hz, 1H), 807 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.20 (br s, 1H), 5.46 (m, 1H), 4.15 (m, 1H), 3.52 (m, 2H), 3.41 (m, 2H), 2.45 (s, 3H) AC24 129-132 526.98 ([M + H]⁺) 7.40 (m, 2H), 7.27 (m, 3298, 1664, 2H), 7.25 (m, 2H), 1113, 803 6.92 (br s, 2H), 6.60 (m, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.19 (d, J = 5.2, 2H), 4.08 (m, 1H), 3.99 (m, 2H), 2.46 (s, 3H) AC25 542.24 ([M − H]⁻) 7.41 (m, 3H), 7.27 (m, 3257, 1652, 2H), 6.58 (d, J = 15.6 Hz, 1316, 1109, 1H), 6.42 (m, 2H), 807 4.92 (m, 1H), 4.65 (m, 2H), 4.14 (m, 1H), 4.09 (m, 2H), 2.46 (s, 3H) AC26 550.69 ([M − H]⁻) 7.45 (s, 1H), 7.40 (s, 3255, 1638, 2H), 7.34 (d, J = 8.0 Hz, 1113, 809 1H), 7.22 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC27 541.00 ([M − H]⁻) 8.46 (d, J = 4.0 Hz, 1H), 1653, 1113, 8.20 (s, 1H), 7.76 (m, 809 1H), 7.47 (m, 2H), 7.41 (s, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.4 Hz, 1H), 4.11 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC28 65-67 564.84 ([M − H]⁻) 8.40 (s, 1H), 7.74 (m, 3267, 1650, 2H), 7.42 (m, 3H), 1112, 809 7.36 (m, 2H), 6.72 (br s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H) AC29 75-78 511.78 ([M − H]⁻) 7.71 (d, J = 8.4 Hz, 1H), 7.42 (m, 3H), 7.35 (m, 1H), 6.75 (br s, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 5.49 (m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC30 110-113 543.72 ([M − H]⁻) 7.42 (d, J = 8.4 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 1H), 7.38 (m, 1H), 7.06 (br s, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 8.0 Hz, 1H), 4.93 (m, 1H), 4.65 (m, 2H), 4.13 (m, 3H) AC31 68-70 610.73 ([M + H]⁺) 8.42 (s, 1H), 7.76 (m, 1H), 7.61 (m, 2H), 7.39 (m, 4H), 6.54-6.39 (m, 3H), 4.66 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC32 78-80 555.89 ([M − H]⁻) 7.61 (m, 2H), 7.40 (m, 3H), 6.54 (m, 2H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.46 (m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC33 182-184 587.68 ([M − H]⁻) 7.62 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.40 (m, 3H), 6.84 (br s, 1H), 6.55 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 7.6 Hz, 1H), 4.93 (m 1H), 4.65 (m, 2H), 4.13 (m, 4H) AC34 151-153 545.83 ([M − H]⁻) 7.67 (s, 1H), 7.61 (d, J = 6.0 Hz, 1H), 7.53 (m, 1H), 7.41 (s, 2H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (br s, 1H), 5.44 (m, 1H), 4.14 (m, 1H), 3.50 (m, 2H), 3.40 (m, 2H) AC35 100-102 577.71 ([M − H]⁻) 7.70 (s, 1H), 7.63 (m, 3257, 1655, 1H), 7.53 (d, J = 7.6 Hz, 1113, 808 1H), 7.41 (s, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.49 (m, 2H), 4.93 (m, 1H), 4.64 (m, 2H), 4.13 (m, 1H), 4.03 (m, 2H) AC36 81-83 600.83 ([M + H]⁺) 8.40 (s, 1H), 7.73 (m, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.35 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (m, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H) AC37 512.68 ([M + H]⁺) 8.39 (s, 1H), 7.73 (m, 3268, 1644, 1H), 7.48 (m, 2H), 1109, 820 7.34 (d, J = 7.6 Hz, 1H), 7.24 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 6.12 (m, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC38 79-80 528.85 ([M − H]⁻) 8.46 (m, 1H), 7.73 (m, 1H), 7.35 (m, 4H), 7.22 (m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.45 (s, 3H) AC39 141-144 477.83 ([M − H]⁻) 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC40 69-72 484.67 ([M + H]⁺) 8.33 (t, J = 5.6 Hz, 1H), 8.61 (m, 1H), 7.68 (m, 3H), 7.48 (m, 2H), 6.86 (dd, J = 15.6, 8.2 Hz 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.44 (m, 1H), 3.76 (d, J = 6.0 Hz, 2H), 2.54 (m, 1H), 2.67 (s, 3H), 0.59 (m, 2H), 0.54 (m, 2H) AC41 196-199 515.00 ([M − H]⁻) 8.66 (d, J = 7.6 Hz, 1H), 8.39 (t, J = 5.6 Hz, 1H), 7.65 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 5.01 (m, 1H), 4.99 (m, 1H), 3.78 (d, J = 6.0 Hz, 2H), 3.40 (m, 2H), 3.22 (m, 2H), 2.37 (m, 3H) AC42 79-82 534.72 ([M + H]⁺) 7.99 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.51 (m, 2H), 7.44 (m, 2H), 7.27 (m, 4H), 6.71 (t, J = 5.2 Hz, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 5.05 (d, J = 1.6 Hz, 2H), 4.12 (m, 1H), 2.52 (m, 3H) AC43 481.75 ([M + H]⁺) 8.69 (s, 1H), 8.52 (s, 1663, 2H), 7.45 (d, J = 7.6 Hz, 1608, 1168, 1H), 7.37 (d, J = 2.0 Hz, 1114, 801 1H), 7.26 (m, 2H), 7.21 (m, 1H), 6.83 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.81 (d, J = 5.6 Hz, 2H), 4.12 (t, J = 8.4 Hz 1H), 2.45 (s, 3H) AC44 528.01 ([M + H]⁺) 8.44 (d, J = 2.4 Hz, 1H), 1640, 1166, 7.69 (d, J = 2.4 Hz, 1112, 800 1H), 7.37 (m, 1H), 7.33 (s, 1H), 7.31 (s, 1H), 7.26 (m, 1H), 7.24 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.32 (t, J = 7.2 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 2.41 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H) AC45 512.88 ([M + H]⁺) 7.66 (s, 1H), 7.37 (d, J = 6.8 Hz, 1657, 1167, 2H), 7.26 (m, 1106, 800 3H), 7.18 (m, 1H), 7.11 (m, 2H), 6.99 (m, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 3.36 (s, 3H), 2.43 (s, 3H) AC46 61-64 575.93 ([M + H]⁺) 8.42 (d, J = 2.0 Hz, 1H), 7.76 (d, J = 2.4 Hz, 1H), 7.61 (m, 2H), 7.39 (m, 3H), 7.26 (s, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 7.6 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H) AC47 525.89 ([M − H]⁻) 10.02 (s, 1H), 9.87 (s, 3280, 1640 1H), 8.47 (t, J = 6.0 Hz, 1H), 7.66 (s, 3H), 7.44 (s, 1H), 7.40 (d, J = 3.6 Hz, 2H), 6.86 (dd, J = 15.6, 9.2 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.82 (t, J = 9.6 Hz, 2H), 3.88 (d, J = 6.0 Hz, 2H), 2.36 (s, 3H), 1.63 (m, 1H), 0.76 (m, 4H) AC48 509.96 ([M − H]⁻) 7.37 (m, 7H), 7.34 (m, 3275, 1642 3H),, 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.01 (m, 1H), 4.60 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.46 (s, 3H) AC49 518.85 ([M + H]⁺) 8.39 (d, J = 2.0 Hz, 1H), 1658, 1112, 8.11 (m, 1H), 7.71 (d, J = 2.4 Hz, 1025, 2219 1H), 7.41 (m, 3H), 7.17 (m, 3H), 6.59 (d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H) AC50 481.88 ([M + H]⁺) 8.72 (m, 1H), 7.67 (s, 1654, 1112, 3H), 7.46 (s, 1H), 800, 3069 7.40 (m, 2H), 7.08 (s, 1H), 6.82 (m, 2H), 6.55 (d, J = 7.6 Hz, 1H), 4.82 (m, 1H), 4.48 (s, 2H), 3.65 (s, 3H), 2.38 (s, 3H) AC51 540.83 ([M + H]⁺) 7.45 (d, J = 7.6 Hz, 1H), 1652, 1571, 7.38 (m, 1H), 7.27 (m, 802, 1114, 2H), 7.22 (m, 2H), 2926 6.85 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.33 (m, 2H), 4.14 (m, 3H), 3.18 (s, 3H), 2.48 (s, 3H) AC52 488.29 ([M − H]⁻) 7.33 (m, 2H), 7.25 (m, 1635, 11134, 3H), 6.56 (d, J = 15.6 Hz, 813, 2927 1H), 6.37 (dd, J = 15.6, 8.0 Hz, 1H), 5.61 (d, J = 8.0 Hz, 1H), 4.21 (m, 1H), 4.01 (m, 1H), 4.08 (m, 2H), 3.56 (t, J = 10.0 Hz, 2H), 2.48 (m, 2H), 2.08 (m, 2H), 1.5 (m, 3H) AC53 532.92 ([M + H]⁺) 8.49 (d, J = 2.0 Hz, 1H), 1651, 3027, 7.69 (d, J = 2.4 Hz, 1H), 815, 1113 7.43 (d, J = 8.0 Hz, 1H), 7.34 (m, 3H), 7.26 (m, 2H), 6.95 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.72 (d, J = 5.2 Hz, 2H), 4.09 (m, 1H), 2.47 (s, 3H) AC54 529.06 ([M − H]⁻) 8.37 (d, J = 5.2 Hz, 1H), 1654, 3434, 7.41 (d, J = 8.0 Hz, 1H), 814, 1112 7.36 (m, 3H), 7.31 (m, 1H), 7.26 (m, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 5.20 (t, J = 5.6 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.18 (s, 3H) AC57 464.96 ([M + H]⁺) 8.69 (t, J = 6.0 Hz, 1H), 3417, 1658, 8.58 (t, J = 6.0 Hz, 1H), 1165, 817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H), 6.76 (dd, J = 15.6, 8.0 Hz, 1H), 4.01 (m, J = 8.0 Hz, 1H), 3.71 (m, 2H), 3.49 (m, 2H) AC58 124.4-126.9 599.76 ([M + H]⁺) 7.62 (m, 2H), 7.40 (s, 2H), 7.37 (d, J = 1.6 Hz, 1H), 6.61 (t, J = 4.8 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.16 (d, J = 6.0 Hz, 2H), 4.01 (m, 1H), 1.56 (s, 9H) AC59 80-83 497.40 ([M − H]⁻) 8.42 (d, J = 2.1 Hz, 1H), 8.29 (d, J = 7.5 Hz, 1H), 7.51 (m, 2H), 7.39 (m, 1H), 7.36 (m, 4H), 7.28 (m, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8 Hz 1H), 4.14 (t, J = 8.4 Hz, 1H), 2.51 (s, 3H) AC60 515.09 ([M + H]⁻) 8.52 (s, 1H), 8.39 (d, J = 1.8 Hz, 1668, 1589, 2H), 7.70 (d, J = 2.1 Hz, 1167, 1113, 1H), 7.62 (s, 802 1H), 7.43 (s, 1H), 7.35 (m, 3H), 6.62 (d, J = 16.2 Hz, 1H), 6.52 (dd, J = 16.2, 7.5 Hz, 1H), 4.62 (d, J = 6.3 Hz, 2H), 4.19 (m, 1H), 2.76 (s, 3H) AC61 461.90 ([M − H]⁻) 8.07 (t, J = 8.0 Hz, 1H), 1658, 1114, 7.39 (t, J = 2.0 Hz, 1H), 801 7.28 (d, J = 1.2 Hz, 3H), 7.17 (d, J = 1.6 Hz, 1H), 7.11 (m, 1H), 6.59 (d, J = 15.6 Hz, 1H), 6.47 (dd, J = 15.6, 7.6 Hz, 1H), 5.49 (m, 1H), 4.14 (t, J = 8.4 Hz, 1H), 3.48 (m, 4H) AC62 105-108 528.88 ([M − H]⁻) 8.62 (t, J = 6.4 Hz, 1H), 8.46 (m, 1H), 7.73 (m, 5H), 7.48 (d, J = 7.6 Hz, 1H), 7.03 (dd, J = 15.6, 9.2 Hz, 1H), 6.81 (d, J = 15.6 Hz, 1H), 4.86 (m, 1H), 3.97 (m, 4H) AC63 77-80 594.67 ([M + H]⁺) 8.43 (s, 1H), 7.76 (d, J = 2.4 Hz, 3257, 1653 1H), 7.60 (m, 2H), 7.38 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 6.4 Hz, 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.46 (m, 1H), 6.41 (dd, J = 16.0 8.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H) AC64 83-85 580.72 ([M − H]⁻) 7.72 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.05 (t, J = 5.2 Hz, 1H), 6.70 (t, J = 5.2 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.15 (m, 1H), 4.01 (m, 2H) AC65 534.72 ([M − H]⁻) 8.39 (d, J = 2.0 Hz, 1658, 1113, 1H), 8.12 (t, J = 8.4 Hz, 817, 2925 1H), 7.71 (d, J = 2.4 Hz, 1H), 7.34 (m, 3H), 7.26 (m, 1H), 7.11 (m, 2H), 6.59 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.2 Hz, 2H), 4.13 (m, 1H) AC66 73-75 624.61 ([M − H]⁻) 7.88 (s, 1H), 7.63 (d, J = 1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.40 (m, 2H), 6.80 (t, J = 5.6 Hz, 1H), 6.70 (t, J = 5.6 Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 2H), 4.12 (m, 1H), 4.01 (m, 2H) AC67 479.82 ([M − H]⁻) 8.07 (t, J = 8.0 Hz, 1H), 3272, 1644 7.34 (d, J = 6.0 Hz, 2H), 7.28 (s, 1H), 7.17 (s, 2H), 6.59 (d, J = 15.6 Hz, 1H), 6.46 (dd, J = 15.6, 8.0 Hz, 1H), 5.49 (m, 1H),, 4.12 (m, 1H), 3.49 (m, 4H). AC68 90-93 546.80 ([M − H]⁻) 8.6 (t, J = 6.4 Hz, 1H), 3315, 1684 8.45 (m, 1H), 7.86 (d, J = 6.4 Hz, 2H), 7.75 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 12.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.88 (m, 1H), 3.96 (m, 4H) AC69 542.82 ([M − H]⁻) 7.41 (d, J = 8.0 Hz, 1H), 3294, 1685 7.34 (d, J = 5.6 Hz, 2H), 7.26 (m, 1H), 7.23 (m, 1H), 6.81 (s, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.55 (s, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.18 (m, 2H), 4.13 (m, 1H), 3.97 (m, 2H), 2.46 (s, 3H) AC70 176-178 545.23 ([M − H]⁻) 8.38 (d, J = 2.4 Hz, 1H), 8.22 (d, J = 6.8 Hz, 2H), 7.71 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 6.0 Hz, 2H), 7.30 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 1.6 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.6, 7.6 Hz, 1H), 4.66 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 3.98 (s, 3H) AC71 492.20 ([M − H]⁻) 8.24 (d, J = 7.6 Hz, 1H), 1639, 3079, 8.15 (d, J = 8.4 Hz, 1H), 858 7.35 (d, J = 6.0 Hz, 2H), 7.13 (d, J = 1.2 Hz, 1H), 6.92 (s, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H), 5.48 (m, 1H), 4.13 (m, 1H), 4.03 (s, 3H), 3.48 (m, 4H) AC72 543.05 ([M − H]⁻) 8.42 (d, J = 2.4 Hz, 1H), 1642, 3246, 7.75 (d, J = 2.4 Hz, 1H), 814, 1113 7.34 (m, 4H), 7.20 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.12 (t, J = 5.6 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.20 (m, 1H), 2.82 (m, 2H), 1.45 (t, J = 5.6 Hz, 3H) AC75 644.78 ([M + H]⁺) 8.72 (s, 1H), 7.97 (d, J = 7.2 Hz, 3431, 1652, 1H), 7.70 (d, J = 8.4 Hz, 1171, 809 1H), 7.61 (m, 2H), 7.40 (m, 2H), 6.55 (m, 2H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.76 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC76 531.34 ([M + H]⁺) 8.87 (t, J = 6.0 Hz, 1H), 3120, 1708, 8.34 (d, J = 2.1 Hz, 1H), 1171 7.85 (d, J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 9.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.82 (m, 2H), 2.36 (t, J = 5.6 Hz, 3H) AC77 531.1 ([M + H]⁺) 8.87 (t, J = 6.0 Hz, 1H), 3444, 1648, 8.34 (d, J = 2.1 Hz, 1H), 1114, 814 7.85 (d, J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 8.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.36 (s, 3H) AC78 561.06 ([M + H]⁺) 8.59 (t, J = 6.4 Hz, 1H), 3432, 1631, 8.47 (t, J = 5.6 Hz, 1H), 1161, 840 7.89 (s, 2H), 7.45 (m, 3H), 6.87 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (t, J = 8.0 Hz 1H), 3.98 (m, 4H), 2.58 (s, 3H) AC79 610.97 ([M + H]⁺) 8.69 (t, J = 6.0 Hz, 1H), 3303, 1658, 8.58 (t, J = 6.0 Hz, 1H), 1166, 817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H) 4.83 (t, J = 8.0 Hz, 1H), 3.98 (m, 4H) AC80 561.06 ([M + H]⁺) 7.37 (m, 3H), 7.26 (m, 3412, 1624, 1H), 7.24 (m, 1H), 1157, 825 6.59 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.24 (m, 4H), 3.90 (m, 1H), 2.83 (m, 2H), 1.26 (m, 3H) AC81  9-92 546.93 ([M − H]⁻) 8.73 (d, J = 5.6 Hz, 1H), 8.45 (t, J = 6.0 Hz, 1H), 7.76 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 16.0, 9.2 Hz, 1H), 4.83 (m, 1H), 4.56 (m, 2H), 4.51 (m, 1H), 4.10 (m, 2H), 3.85 (d, J = 6.0 Hz, 2H), 2.50 (m, 3H) AC82 477.69 ([M + H]⁺) 7.38 (d, J = 1.8 Hz, 1646, 1353, 2H), 7.33 (s, 1H), 1196, 1112, 7.27 (s, 3H), 6.58 (d, J = 16.0 Hz, 800 1H), 6.42 (d, J = 8.1 Hz, 1H), 6.36 (dd, J = 16.0, 7.8 Hz, 1H), 4.71 (m, 1H), 4.23 (m, 3H), 3.26 (m, 2H), 2.45 (s, 3H) AC83 493.83 ([M − H]⁻) 8.07 (t, J = 8.4 Hz, 1H), 1527, 1113, 7.39 (t, J = 1.6 Hz, 1H), 801, 1167, 7.31 (d, J = 1.2 Hz, 1H), 1321 7.26 (m, 2H), 7.23 (m, 1H), 7.19 (d, J = 1.6 Hz, 1H), 6.60 (d, J = 16.8 Hz, 1H), 6.49 (dd, J = 16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H), 4.10 (m, 1H) AC84 511.75 ([M − H]⁻) 8.07 (t, J = 8.0 Hz, 1H), 1645, 1113, 7.34 (m, 3H), 7.19 (d, J = 13.2 Hz, 804, 3030, 1H), 6.60 (d, 1245 J = 16.4 Hz, 1H), 6.48 (dd, J = 16.4, 8.0 Hz, 1H), 4.88 (m, 1H), 4.62 (m, 2H), 4.12 (m, 3H) AC85 523.83 ([M − H]⁻) 8.60 (d, J = 6.8 Hz, 1H), 1652, 3039, 8.15 (d, J = 8.4 Hz, 1H), 802, 1114 7.35 (d, J = 6.0 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.94 (s, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 7.6, 7.6 Hz, 1H), 4.93 (m, 1H), 4.62 (m, 2H), 4.13 (m, 6H) AC86 524.36 ([M + H]⁺) 7.35 (d, J = 6.3 Hz, 3H), 3333, 1651, 7.26 (m, 2H), 7.20 (m, 815 1H), 6.60 (d, J = 15.9 Hz, 1H), 6.47 (dd, J = 15.9, 6.6 Hz, 1H), 4.86 (m, 1H), 4.65 (m, 2H), 4.13 (m, 3H), 2.84 (q, 2.8 Hz, 2H), 1.26 (m, 3H) AC87 495.82 ([M − H]⁻) 8.07 (t, J = 8.0 Hz, 1H), 1623, 1114, 7.52 (m, 3H), 7.19 (d, J = 13.2 Hz, 816 1H), 6.59 (d, J = 16.4 Hz, 1H), 6.47 (dd, J = 16.4, 8.0 Hz, 1H), 4.69 (m, 1H), 4.23 (m, 3H), 3.29 (m, 2H) AC89 509.89 ([M + H]⁺) 7.43 (m, 2H), 7.27 (m, 1666, 1166, 2H), 7.23 (m, 2H), 1112, 800 6.58 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.79 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H) AC90 656.9 ([M − H]⁻) 8.34 (m, 1H), 8.27 (m, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.40 (s, 2H), 7.36 (dd, J = 8.2, 1.7 Hz, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 15.9, 7.9 Hz, 1H), 4.89 (d, J = 8.4 Hz, 2H), 4.48 (d, J = 9.0 Hz, 2H), 4.11 (m, 1H) AC91 640.9 ([M − H]⁻) 8.18 (t, J = 5.0 Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J = 8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, J = 15.9, 7.9 Hz, 1H), 4.54 (d, J = 4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, J = 8.9, 6.5 Hz, 2H) AC92 640.9 ([M − H]⁻) 9.16 (d, J = 6.1 Hz, 1H), 7.65 (d, J = 1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J = 5.6 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 7.8 Hz, 1H), 4.59 (d, J = 5.6 Hz, 2H), 4.45 (qd, J = 9.0, 6.0 Hz, 2H), 4.12 (q, J = 7.2 Hz, 1H) AC93 485.5 ([M + H]⁺) 7.52-7.41 (d, J = 8.2 Hz, ¹³C NMR (δ)³ 1H), 7.39-7.34 (m, 1H), 169.91, 7.24-7.17 (d, J = 1.8 Hz, 169.84, 2H), 7.02-6.92 (m, 2H), 138.23, 6.90-6.83 (d, J = 11.4 Hz, 137.41, 1H), 6.71 (br s, 1H), 136.84, 6.17 (br s, 1H), 134.79, 6.12-6.01 (dd, J = 11.4, 10.3 Hz, 134.69, 1H), 4.44-4.38 (d, J = 4.2 Hz, 131.07, 1H), 128.69, 4.35-4.27 (m, 1H), 4.10-3.99 (d, J = 5.1 Hz, 127.49, 2H), 127.43, 2.78-2.67 (m, 1H), 2.44 (s, 3H), 126.72, 0.88-0.78 (m, 2H), 126.61 (q, J = 212.10 Hz), 0.60-0.45 (m, 2H) 125.61, 123.76, 47.89 (q, J = 28.28 Hz), 43.46, 22.65, 19.97, 8.21 AC94 511.6 ([M]⁻) 8.36-8.24 (d, J = 2.4 Hz, 3262, 1607, 1H), 7.75-7.64 (m, 1247, 1164, 1H), 7.38-7.24 (m, 1111 3H), 7.24-7.09 (d, J = 1.8 Hz, 2H), 6.99-6.90 (m, 2H), 6.89-6.74 (d, J = 11.4 Hz, 1H), 6.63-6.43 (m, 1H), 6.14-5.98 (m, 1H), 4.69-4.51 (d, J = 6.1 Hz, 2H), 4.37-4.20 (m, 1H), 2.46-2.31 (s, 3H) AC95 48-61 626.9 ([M + H]⁺) 7.58 (d, J = 7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14 (dd, J = 7.9, 1.6 Hz, 1H), 6.86 (d, J = 11.4 Hz, 1H), 6.76 (t, J = 5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J = 5.5 Hz, 1H), 3.98 (qd, J = 9.0, 6.5 Hz, 2H) AC96 619.6 ([M + H]⁺) 8.83 (s, 1H), 8.06 (br, 1616, 1114 1H), 7.90 (s, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.53 (m, 1H), 6.94 (m, 1H), 6.77 (d, J = 15.3 Hz, 1H), 6.63 (d, J = 9.3 Hz, 1H), 4.84 (m, 1H), 4.30 (d, J = 5.6 Hz, 2H), 2.99 (s, 6H) AC97 606.6 ([M + H]⁺) 8.20 (d, J = 2.1 Hz, 1644, 1113 1H), 7.73 (d, J = 2.7 Hz, 1H), 7.60 (m, 2H), 7.39 (s, 2H), 7.29 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.40 (m, 2H), 4.60 (d, J = 2.7 Hz, 2H), 4.13 (m, 1H), 3.95 (s, 3H) AC98 577.87 ([M + H]⁺) 9.04 (t, J = 6.0 Hz, 1H), 1663, 1168 8.60 (t, J = 6.6 Hz, 1H), 8.25 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 6.3 Hz, 2H), 7.69 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.86 (m, 1H), 3.98 (m, 4H). AC99 574.81 ([M + H]⁺) 8.69 (t, J = 6.0 Hz, 1H), 1650, 1164 8.58 (t, J = 6.6 Hz, 1H), 7.91 (s, 1H), 7.85 (m, 1H), 7.61 (m, 2H), 7.52 (m, 2H), 6.98 (dd, J = 15.3, 9.0 Hz, 1H), 6.76 (d, J = 15.3 Hz, 1H), 4.81 (m, 1H), 4.01 (m, 4H) AC100 673.80 ([M + H]⁺) 8.29 (s, 1H), 8.22 (d, J = 8.1 Hz, 3403, 1659 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.72 (m, 1H), 7.65 (m, 2H), 7.40 (s, 2H), 7.18 (br, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H), 5.02 (d, J = 1.2 Hz, 2H), 4.12 (m, 1H) AC101 636.83 ([M + H]⁺) 7.56 (d, J = 9.0 Hz, 1637, 1113 1H), 7.39 (d, J = 6.0 Hz, 2H), 7.26 (m, 2H), 6.54 (d, J = 15.9 Hz, 1H), 6.37 (dd, J = 8.0, 15.9 Hz, 1H), 4.01 (m, 1H), 3.84 (m, 2H), 3.33 (m, 2H), 3.04 (m, 2H), 2.84 (m, 3H), 2.62 (m, 1H) AC102 592.84 ([M + H]⁺) 7.60 (m, 2H), 7.32 (m, 1668, 1167 1H), 7.03 (d, J = 7.2 Hz, 2H), 6.74 (br, 1H), 6.62 (br, 1H), 6.56 (d, J = 16.2 Hz, 1H), 6.41 (dd, J = 16.2, 7.8 Hz, 1H), 4.22 (d, J = 5.4 Hz, 2H), 4.14 (m, 1H), 4.01 (m, 2H) AC103  99.2-105.0 612.7 ([M + H]⁺) 8.40 (d, J = 8.0 Hz, 1H), 1634, 1113, 7.92 (d, J = 5.2 Hz, 1H), 809 7.59 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0, 7.6 Hz, 1H), 6.76 (d, J = 16.0 Hz, 1H), 4.84 (m, 1H), 4.23 (d, J = 13.2 Hz, 1H), 3.97 (m, 1H), 3.79 (d, J = 13.6 Hz, 1H), 3.16 (t, J = 11.2 Hz, 1H), 2.77 (t, J = 11.2 Hz, 1H), 1.99 (s, 3H), 1.88 (m, 2H), 1.45 (m, 2H) AC104 680.97 ([M + H]⁺) 7.60 (m, 2H), 7.40 (m 3437, 3H), 6.55 (d, J = 15.6 Hz, 1644, 1H), 6.41 (dd, J = 15.6, 1113, 7.8 Hz, 1H), 807, 4.24 (m, 1H), 3.34 (m, 2H), 511 2.90 (m, 1H), 2.24 (m, 2H), 1.52 (m, 2H), 1.34 (m, 4H) AC105 609.9 ([M + H]⁺) 7.59 (s, 1H), 7.55 (m, 3303, 1649, 1H), 7.50 (m, 1H), 1115, 2242, 7.40 (m, 2H), 6.54 (d, J = 16.0 Hz, 809, 506 1H), 6.50 (J = 16.0, 8.0 Hz, 1H), 4.14 (m, 2H), 3.08 (m, 4H), 2.67 (m, 2H), 2.12 (m, 2H), 1.70 (m, 2H). AC106 584.95 ([M + H]⁺) 7.59 (s, 1H), 7.51 (d, J = 8.4 Hz, 3417, 1H), 7.40 (s, 1648, 2H), 7.36 (d, J = 6.8 Hz, 1112, 1H), 6.54 (d, J = 16.0 Hz, 805, 555 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (d, J = 8.0 Hz, 1H), 4.11 (m, 2H), 3.10 (m, 2H), 2.50 (m, 2H), 2.50 (s, 3H) (m, 2H), 1.94 (m, 2H) AC107 609.9 ([M + H]⁺) 8.41 (d, J = 7.8 Hz, 1H), 3303, 7.90 (s, 2H), 7.62 (m, 1645, 2H), 7.51 (m, 1H), 1115, 6.92 (dd, J = 15.9, 9.0 Hz, 2243, 1H), 6.77 (d, J = 15.9 Hz, 810, 1H), 4.81 (m, 1H), 507 3.73 (s, 2H), 3.31 (m, 1H), 3.28 (m, 1H), 2.82 (t, J = 11.4 Hz, 2H), 2.82 (m, 2H), 2.30 (m, 2H), 1.88 (m, 2H), 1.57 (m, 2H) AC108 626.9 ([M + H]⁺) 7.60 (m, 2H) 7.39 (s, 3420, 2H), 7.28 (m, 1H), 1649, 6.56 (d, J = 15.6 Hz, 1H), 1113, 6.40 (dd, J = 15.6, 7.8 Hz, 809, 1H), 5.91 (m, 1H), 554 4.65 (m, 2H), 4.10 (m, 1H), 4.07 (m, 2H), 3.59 (m, 1H), 2.74 (m, 2H), 2.13 (m, 4H), 2.07 (m, 1H) AC109 614.6 ([M + H]⁺) 7.56 (m, 2H), 7.39 (s, 1647, 1113 2H), 7.29 (s, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 8.0 Hz 1H), 4.09 (m, 1H), 3.88 (m, 2H), 3.49 (m, 2H), 2.92 (m, 2H), 2.81 (m, 1H), 2.74 (m, 2H), 2.25 (m, 4H) AC110 572.6 ([M + H]⁺) 11.20 (s, 1H), 8.66 (br, 3412, 1690, 1H), 7.92 (m, 3H), 1114, 846, 7.62 (d, J = 8.0 Hz, 1H), 559 7.45 (d, J = 8.0 Hz, 1H), 6.77 (dd, J = 15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.74 (d, J = 5.2 Hz, 2H), 3.61 (s, 3H) AC111 582.79 ([M + H]⁺) 8.63 (t, J = 6.0 Hz, 1H), 3419, 1659, 8.04 (t, J = 6.0 Hz, 1H), 843, 557 7.92 (m, 3H), 7.62 (d, J = 1.2 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.00 (dd, J = 15.6, 8.8 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 5.19 (d, J = 1.6 Hz, 1H), 5.01 (d, J = 1.2 Hz, 1H), 4.85 (m, 1H), 3.86 (d, J = 5.6 Hz, 2H), 3.75 (t, J = 5.6 Hz, 2H) AC112 582.79 ([M + H]⁺) 8.84 (br, 1H), 8.58 (m, 3399, 1662, 1H), 8.30 (m, 1H), 1114, 807, 7.91 (s, 2H), 7.61 (d, J = 8.1 Hz, 582 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.6, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 4.11 (d, J = 5.6 Hz, 1H), 3.73 (d, J = 5.6 Hz, 1H), 3.04 (s, 6H) AC113 626.88 ([M + H]⁺) 8.48 (t, J = 5.2 Hz, 1H), 3431, 1651, 8.3 (s, 1H), 7.90 (s, 2H), 1113, 808, 7.79 (dd, J = 2.0, 2.0 Hz 554 2H), 7.58 (d, J = 8.4 Hz, 1H) 7.46 (d, J = 7.6 Hz, 1H) 7.26 (d, J = 7.6 Hz, 1H), 6.98 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.49 (d, J = 6.4 Hz, 2H) 2.87 (t, J = 6.4 Hz, 2H) AC114 113.7-117.5 570.7 ([M + H]⁺) 8.77 (s, 1H), 8.58 (d, J = 7.2 Hz, 2H), 7.93 (d, J = 7.2 Hz, 2H), 7.60 (dd, J = 1.2, 0.8 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 6.99 (m, 1H), 6.77 (d, J = 16 Hz, 1H), 4.85 (m, 1H), 4.10 (m, 1H) 3.29 (m, 2H), 3.05 (m, 2H), 2.0 (m, 2H), 1.76 (m, 2H) AC115 529.00 ([M + H]⁺) 8.43 (s, 1H), 7.79 (d, J = 8.0 Hz, 1589, 3459, 1H), 7.51 (m, 801, 1110 1H), 7.36 (d, J = 8.4 Hz, 3H), 7.21 (m, 3H), 6.55 (d, J = 15.6 Hz, 1H), 6.36 (dd, J = 15.6, 8.0 Hz, 1H), 5.04 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 2.35 (s, 3H) AC116 614.87 ([M + H]⁺) 7.99 (d, J = 8.4 Hz, 1H), 3424, 1657, 7.46 (d, J = 1.6 Hz, 1H), 1165 7.34 (d, J = 6.4 Hz, 2H), 7.28 (m, 2H), 6.62 (m, 2H), 6.47 (dd, J = 16.0, 7.2 Hz, 1H), 4.23 (m, 2H), 4.12 (m, 1H), 4.00 (m, 2H) AC117 525.42 ([M − H]⁻) 8.39 (br, 1H), 7.85 (br, 3401, 1636, 1H), 7.62 (m, 3H), 1113, 750 7.53 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.17 (m, 1H), 6.78 (dd, J = 16.0, 8.8 Hz, 1H), 6.70 (m, 1H), 4.77 (m, 1H), 4.66 (s, 1H), 4.32 (s, 1H), 2.97 (s, 3H), 2.16 (s, 3H) AC118 471.79 ([M + H]⁺) 7.36 (d, J = 8.0 Hz, 2H), 3437, 1655, 7.27 (m, 2H), 7.22 (m, 1262, 1105, 2H), 6.57 (d, J = 16.0 Hz, 802 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br, 1H), 4.15 (m, 2H), 3.89 (m, 1H), 3.80 (m, 2H), 3.35 (m, 1H), 2.46 (s, 3H), 2.06 (s, 1H), 1.96 (m, 2H), 1.65 (m, 1H) BC1 492.17 ([M + H]⁺) 7.39 (s, 2H), 3211, 1569, 7.25-7.18 (m, 3H), 6.58 (d, J = 16.0 Hz, 1113, 806 1H), 6.30 (dd, J = 16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05-2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H) BC2 506.4 ([M + H]⁺) 8.80 (s, 1H), 8.20 (s, 2923, 1542, 1H), 7.82 (m, 3H), 1033, 805 7.4 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H), 3.38 (m, 2H), 2.98 (m, 2H), 2.71 (m, 1H), 2.04 (m, 2H), 1.54 (s, 3H). BC3 518.04 ([M − H]⁻) 7.40 (s, 2H), 3120, 1592, 7.33-7.22 (m, 3H), 6.61 (d, J = 16.0 Hz, 1146, 895 1H), 6.34-6.28 (dd, J = 16.0, 8.0 Hz, 1H), 5.96-5.80 (m, 3H), 5.22 (m, 4H), 4.01 (m, 2H), 2.84-2.99 (m, 2H), 2.71 (m, 1H), 1.86 (m, 1H) BC4 529.02 ([M + H]⁺) 7.39 (s, 2H), 3283, 1652, 7.25-7.20 (m, 3H), 6.34 (d, J = 16.0 Hz, 1241, 811 1H), 6.30 (dd, J = 16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); BC5 544.25 ([M − H]⁻) 7.40 (s, 2H), 7.21 (s, 3489, 3291, 1H), 7.12 (m, 1H), 1655, 1112, 6.56 (d, J = 16.0 Hz, 1H), 808 6.32 (dd, J = 16.0, 8.4 Hz, 1H), 5.85 (br s, 1H), 5.23 (br s, 1H), 4.12 (m, 1H), 3.18 (m, 3H), 2.80 (m, 3H), 2.08 (m, 2H), 1.83 (m, 5H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC6 485.96 ([M − H]⁻) 7.40 (s, 2H), 3429, 1114, 7.31-7.18 (m, 3H), 6.58 (d, J = 16.0 Hz, 804 1H), 6.24-6.28 (dd, J = 16.0, 8.0 Hz, 1H), 5.40 (br, 1H), 4.01 (m, 2H), 2.78-3.01 (m, 2H), 2.51 (s, 1H), 1.86 (m, 1H), 1.20 (m, 2H), 1.01 (m, 2H), 0.78 (m, 2H) BC7 500.01 ([M − H]⁻) 7.40 (s, 2H), 7.31 (s, 3296, 1115, 1H), 7.18 (m, 1H), 806 7.18 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (dd, J = 16.0, 8.0 Hz, 1H), 5.78 (br s, 1H), 5.21 (br s, 1H), 4.01 (m, 1H), 2.78 (m, 2H), 2.01 (m, 1H), 1.86 (m, 4H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC8 511.88 ([M − H]⁻) 7.38-7.20 (m, 5H), 1657, 1113, 6.62 (d, J = 16.0 Hz, 1H), 855 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.12 (m, 2H), 3.06-2.82 (m, 2H), 2.75 (m, 1H), 1.85 (m, 1H) BC9 179-181 556.83 ([M − H]⁻) 8.30 (s, 1H), 7.68 (d, J = 6.4 Hz, 1H), 7.38-7.20 (m, 5H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.63 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.56 (s, 2H), 3.06-2.82 (m, 2H), 2.70 (m, 1H), 1.82 (m, 1H) BC10 497.98 ([M − H]⁻) 7.38-7.20 (m, 5H), 3027, 1654, 6.62 (d, J = 16.0 Hz, 1H), 815 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 3H), 1.82 (m, 1H), 1.42 (m, 1H) BC11 530.09 ([M − H]⁻) 7.80 (m, 1H), 7.48 (m, 1715, 1113, 2H), 7.32 6.65 (d, J = 16.0 Hz, 816 1H), 6.54 (dd, J = 16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H), 2.86 (m, 1H), 1.81 (m, 1H) BC12 514.86 ([M + H]⁺) 7.32, (d, J = 6.0 Hz, 2H) 3428, 1112, 7.28 (m, 1H), 7.20 (d, J = 8.0, 857 1H), 7.14 (d, J = 8.8, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); BC13 121-126 553.06 ([M − H]⁻) 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 3H), 6.72 (d, J = 3.6, 1H), 6.39 (m, 1H), 4.71 (t, J = 7.2 Hz, 2H), 4.15 (m, 2H) BC14 172-175 554.0 ([M − H]⁻) 8.83 (t, J = 6.6 Hz, 1H), 8.42 (t, J = 14.7 Hz, 1H), 8.22 (d, J = 8.1 Hz, 1H), 8.13 (t, J = 6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H) CC1 107-109 402.00 ([M + H]⁺) 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, J = 6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H) CC2 118-120 428.11 ([M + H]⁺) 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 1.40 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC3 119-122 468.20 ([M − H]⁻) 7.38 (m, 3H), 7.27 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.4 Hz, 1H), 5.00 (br s, 1H), 4.48 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 3.15 (q, J = 10.4 Hz, 2H) CC4 414.16 ([M − H]⁻) 7.37 (m, 3H), 7.28 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 5.69 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 2.29 (q, J = 5.8 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H) CC5 460.28 ([M − H]⁻) 7.40 (m, 3H), 7.28 (m, 2H), 6.60 (d, J = 15.6 Hz, 1H), 6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.84 (br s, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC6 106-108 504.08 ([M − H]⁻) 7.40 (m, 3H), 7.26 (m, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.96 (br s, 1H), 4.49 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 3.15 (q, J = 10.8 Hz, 2H) CC7 127-128 436.03 ([M + H]⁺) 7.42 (m, 4H), 7.24 (m, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H) CC8 129-131 462.15 ([M + H]⁺) 8.58 (t, J = 5.6 Hz, 1H), 7.72 (m, 1H), 7.66 (m, 3H), 7.49 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 6.90 (dd, J = 16.0, 8.0 Hz, 1H), 6.73 (d, J = 16 Hz, 1H), 4.81 (m, 1H), 4.33 (d, J = 6.0 Hz, 1H), 1.64 (m, 1H), 0.68 (m, 4H) CC9 132-134 504.25 ([M + H]⁺) 7.41 (m, 3H), 7.26 (m, 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 3.13 (m, 2H) CC10 538.03 ([M + 2H]⁺) 7.38 (m, 4H), 6.56 (d, J = 16.0 Hz, 1651, 1112, 1H), 807 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.58 (m, 2H), 4.08 (m, 1H), 3.08 (m, 2H) CC11 111-112 494.12 ([M − H]⁻) 7.42 (m, 3H), 7.24 (m, 1H), 6.54 (d, J = 15.6 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (m, 1H), 4.53 (d, J = 6.0 Hz, 1H), 4.10 (m, 1H), 1.39 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC12 76-78 510.07 ([M − H]⁻) 7.39 (s, 4H), 7.34 (d, J = 8.0 Hz, 1H), 7.26 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br s, 1H), 4.49 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.20 (s, 9H) CC13 73-76 563.37 ([M − H]⁻) 8.51 (d, J = 5.2 Hz, 1H), 7.63 (s, 1H), 7.51 (m, 1H), 7.45 (m, 2H), 7.39 (s, 2H), 7.28 (m, 1H), 6.58 (m, 2H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H) CC14 581.45 ([M + 1H]⁺) 8.51 (m, 1H), 8.30 (d, J = 2.4 Hz, 3430, 1656, 1H), 7.73 (m, 1109, 806 1H), 7.61 (s, 2H), 7.51 (s, 1H), 7.32 (m, 3H), 6.66 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0, 8.4 Hz, 1H), 4.50 (m, 1H), 4.45 (d, J = 5.6 Hz, 1H), 3.56 (s, 2H) CC15 480.24 ([M + H]⁺) 7.40 (m, 3H), 7.33 (m, 3293, 1651, 1H), 7.22 (m, 2H), 1543, 1114, 6.54 (d, J = 15.6 Hz, 1H), 812 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 1.41 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC16 520.33 ([M − H]⁻) 7.42 (s, 1H), 7.37 (m, 3307, 1665, 3H), 7.22 (m, 1H), 1114, 813 6.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.19 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 3.33 (m, 2H) CC17 117-119 459.83 ([M − H]⁻) 7.51 (m, 2H), 7.39 (m, 3293, 1633, 2H), 7.24 (m, 2H), 1110, 820 6.52 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 7.6 Hz, 1H), 6.02 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H), 1.38 (m, 1H)), 1.00 (m, 2H), 0.77 (m, 2H) CC18 119-123 501.88 ([M − H]⁻) 7.48 (m, 2H), 7.41 (s, 3435, 1644, 1H), 7.36 (d, J = 8.0 Hz, 1111, 817 1H), 7.23 (m, 2H), 6.52 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H), 3.13 (m, 2H) CC19 530 ([M + H]⁺) 7.41 (m, 2H), 7.24 (m, 3435, 1644, 1H), 6.53 (d, J = 16.0 Hz, 1111, 817 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.97 (s, 3H), 2.78 (m, 2H) CC20 512 ([M + H]⁺) 7.42 (m, 3H), 7.24 (m, 3293, 1633, 1H), 6.54 (d, J = 15.6 Hz, 1110, 820 1H), 6.34 (dd, J = 15.6, 8.0 Hz, 1H), 6.03 (m 1H), 4.53 (d, J = 6.0 Hz, 1H), 4.10 (m, 1H), 1.19 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC21 55-58 493.99 ([M − H]⁻) (DMSO-d₆) 8.62 (m, 1H), 7.95 (s, 1H), 7.85 (m, 1H), 7.66 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 8.0 Hz, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.83 (m, 1H), 4.44 (s, 2H), 1.68 (m, 1H), 0.71 (m, 4H) CC22 67-69 530.01 ([M + H]⁺) 8.62 (m, 1H), 7.90 (s, 3H), 7.82 (m, 1H), 7.45 (m, 1H), 6.98 (m, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.82 (m, 1H), 4.4 (s, 2H), 1.66 (m, 1H), 0.72 (m, 4H) CC23 69-71 564.99 ([M − H]⁻) 9.02 (br s, 1H), 8.54 (br s, 1H), 8.26 (br s, 1H), 7.48-7.54 (m, 3H), 7.22-7.42 (m, 3H), 6.59-6.62 (m, 2H), 6.38-6.42 (m, 1H), 4.82 (m, 2H), 4.19 (s, 1H) CC24 125-127 570.26 ([M − H]⁻) 7.64 (s, 1H), 7.54 (s, 2H), 7.46 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.4 Hz, 1H), 6.03 (m, 1H), 4.65 (d, J = 6.4 Hz, 2H), 4.14 (m, 1H,), 3.13 (q, J = 10.6 Hz, 2H) CC25 579.86 ([M − H]⁻) 7.60 (s, 1H), 7.40 (s, 3297, 1663, 2H), 7.37 (d, J = 8.0 Hz, 1114, 809 1H), 7.31 (d, J = 8.0 Hz, 1H), 6.53 (d, 1H, J = 16.0 Hz), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 4.56 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H), 3.15 (q, J = 10.6 Hz, 2H) CC26 129-131 539.89 ([M + H]⁺) 7.59 (s, 1H), 7.39 (m, 2H), 7.30 (s, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s, 1H), 4.42 (d, J = 4.4 Hz, 2H), 4.12 (m, 1H), 1.35 (br s, 1H), 0.95 (br s, 2H), 0.75 (m, 2H) CC27 519.95 ([M − H]⁻) 7.39 (s, 2H), 7.33 (t, J = 7.6 Hz, 3306, 1786 1H), 7.14 (m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 7.6 Hz, 1H), 6.06 (br s, 1H), 4.52 (d, J = 16.0 Hz, 2H), 4.08 (m, 1H), 3.90 (s, 2H), 3.13 (m, 2H) CC28 477.93 ([M − H]⁻) 7.39 (s, 2H), 7.35 (m, 3625, 1747 1H), 7.14 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.93 (br s, 1H), 4.49 (d, J = 16.0 Hz, 2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC29 620.86 ([M − H]⁻) 8.58 (d, J = 4.6 Hz, 1H), 1645, 1115, 7.74 (m, 1H), 7.62 (m, 808 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J = 10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H) CC30 101-104 559.75 ([M − H]⁻) 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H) CC31 177-178 463 ([M − H]⁻) 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); CC32 141-142 532.99 ([M + H]⁺) 7.66 (m, 2H), 7.54 (m, 1H), 7.41 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.59 (s, 3H), 4.19 (m, 1H), 3.25 (m, 2H), 1.15 (m, 2H) CC33 540.88 ([M − H]⁻) 7.57 (s, 1H), 7.40 (m, 3338, 1631, 2H), 7.30 (s, 1H), 1578, 1114, 7.20 (br s, 1H), 6.53 (d, J = 16.0 Hz, 809 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s, 1H), 4.75 (br s, 1H), 4.42 (s, 2H), 4.20 (br s, 1H), 4.15 (m, 2H), 3.20 (m, 2H), 1.15 (m, 3H) CC34 118-120 541.40 ([M + H]⁺) 7.42 (m, 3H), 7.28 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 4.96 (m, 1H), 4.51 (d, J = 5.6 Hz, 2H), 4.12 (m, 1H), 3.69 (t, J = 4.8 Hz, 4H), 3.35 (t, J = 4.8 Hz, 1H) CC35 78-79 547.82 ([M + H]⁺) 9.95 (br s, 1H), 8.17 (d, J = 4.8 Hz, 1H), 7.61 (d, J = 6.4 Hz), 7.43 (m, 3H), 7.24 (m, 2H), 6.90 (t, J = 5.6 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.09 (m, 1H) CC36 497 ([M − H]⁻) 7.39 (m, 4H), 7.28 (m, 3350, 1705, 1H), 6.54 (d, J = 16.0 Hz, 1114, 808 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H) CC37 88-91 515.01 ([M + H]⁺) 7.49 (d, J = 8 Hz, 1H), 7.41 (d, J = 7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J = 16 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.0 (brs, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H) CC38 63-66 526.97 ([M + H]⁺) 7.48 (d, J = 8 Hz, 1H), 7.39 (m, 3H), 7.27 (m, 1H), 6.54 (d, J = 16 Hz, 1H), 6.33 (dd, J = 6.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 5.92 (br s, 1H), 5.83 (m, 2H), 5.29 (t, J = 15.4 Hz, 2H), 4.80 (br s, 2H), 4.12 (m, 1H), 4.02 (br s, 2H) CC39 526.09 ([M − H]⁻) 7.39 (m, 4H), 7.28 (m, 3350, 1705, 1H), 6.54 (d, J = 16.0 Hz, 1114, 808 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H) CC40 159-160 580.25 ([M − H]⁻) 7.46 (m, 5H), 7.29 (m, 1H), 7.20 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 5.62 (br s, 1H), 4.55 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC41 512.22 ([M − H]⁻) 7.48 (m, 1H), 7.43 (m, 1740, 1701, 3H), 7.38 (m, 1H), 1114, 808 7.23 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 4.60 (d, 2H), 4.18 (m, 1H), 3.85 (s, 3H) CC42 161-163 578.96 ([M − H]⁻) (DMSO-d₆) 9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (br s, 1H), 7.28 (br s, 1H), 6.93 (m, 1H), 6.75 (br s, 1H), 4.80 (m, 1H), 4.40 (br s, 2H), 3.90 (br s, 2H) CC43 140-142 505.39 ([M + H]⁺) 8.11 (d, J = 4.0 Hz, 1H), 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H) 4.61 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC44 536.88 ([M − H]⁻) 8.41 (s, 1H), 7.77 (s, 3320, 1674, 1H), 7.47 (br s, 1H), 1114, 808 7.40 (s, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.68 (d, J = 4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J = 10.8 Hz, 2H) CC45 494.88 ([M − H]⁻) 8.41 (s, 1H), 7.76 (s, 3309, 1659, 1H), 7.40 (s, 2H), 1115, 808 7.15 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.67 (d, J = 4.4 Hz, 2H), 4.16 (m, 1H), 1.57 (m, 1H), 1.04 (m, 2H), 0.87 (m, 2H) CC46 151-153 554.04 ([M − H]⁻) 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H) CC47 478.09 ([M + H]⁺) 8.06 (m, 2H), 7.61 (m, 3309, 1659, 4H), 7.48 (s, 2H), 1115, 808 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC48 511.05 ([M + H]⁺) 8.06 (m, 2H), 7.61 (m, 3309, 1659, 3H), 7.48 (s, 2H), 1115, 808 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC49 84-87 515.33 ([M + H]⁺). 8.06 (m, 1H), 7.98 (m, 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J = 4.6 Hz, 3H) CC50 138-140 461.32 ([M − 1H]⁻) 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.65 (d, J = 15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, J = 15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); CC51 149-150 505.31 ([M − H]⁻) 7.56 (br s, 1H), 7.4 (s, 3H), 7.3 (m, 3H), 7.05 (br s, 1H), 6.8 (d, J = 6 Hz, 2H), 6.57 (m, 2H), 6.20 (m, 2H), 4.05 (m, 1H), 3.2 (q, J = 10.4 Hz, 2H) CC52 464.87 ([M − H]⁻) 7.40 (s, 2H), 7.18 (s, 3309, 1659, 1H), 7.08 (s, 1H), 1115, 808 6.85 (m, 1H), 6.45 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.30-1.10 (m, 4H), 1.90 (m, 1H) CC53 506 ([M + H]⁺) 7.40 (s, 2H), 7.18 (s, 3309, 1659, 1H), 7.08 (s, 1H), 1115, 808 6.85 (m, 1H), 6.45 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 3.21 (m, 2H) CC54 504 ([M + H]⁺) 7.28 (s, 2H), 7.25 (m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J = 5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J = 7.5 Hz, 2H) DC1 93-97 398.05 ([M + H]⁺) 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.2 Hz, 1H), 4.15 (m, 1H) DC2 363.0746 (363.075) 8.59 (s, 1H), 8.13 (s, 3121, 1524, 1H), 7.69 (d, J = 8.5 Hz, 1251, 1165, 2H), 7.55 (d, J = 8.5 Hz, 1119 2H), 7.41-7.29 (m, 4H), 6.64 (d, J = 15.7 Hz, 1H), 6.47 (dd, J = 15.9, 8.0 Hz, 1H), 4.17 (m, 1H) DC3 329.1144 (329.114) 8.56 (s, 1H), 8.11 (s, 1521, 1246, 1H), 7.65 (d, J = 8.4 Hz, 1219, 1162, 2H), 7.52 (d, J = 8.3 Hz, 1152, 1107 2H), 7.40 (m, 5H), 6.61 (d, J = 15.8 Hz, 1H), 6.51 (dd, J = 15.9, 7.7 Hz, 1H), 4.18 (m, 1H) DC4 364.11 ([M + H]⁺) 8.56 (s, 1H), 8.10 (s, 3147, 1528, 1H), 7.66 (d, J = 2.0 Hz, 1494, 1246, 2H), 7.52 (d, J = 8.8 Hz, 1165, 1108 2H), 7.38 (d, J = 2.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H) DC5 344.25 ([M + H]⁺) 8.54 (s, 1H), 8.10 (s, 3122, 3047, 1H), 7.62 (d, J = 8.3 Hz, 1523, 1252, 2H), 7.50 (d, J = 8.4 Hz, 1160, 1107 2H), 7.25 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.37 (s, 3H) DC6 360.28 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 3124, 2936, 1H), 7.65 (d, J = 8.8 Hz, 1522, 1249, 2H), 7.52 (d, J = 8.8 Hz, 1160 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0, 7.4 Hz, 1H), 4.15 (m, 1H), 3.82 (s, 3H) DC7 348 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 3141, 1512, 1H), 7.62 (d, J = 8.8 Hz, 1246, 1118 2H), 7.5 (d, J = 8.4 Hz, 2H), 7.38 (m, 2H), 7.12 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H) DC8 366.13 ([M + H]⁺) 8.57 (s, 1H), 8.11 (s, 3116, 1628, 1H), 7.65 (d, J = 7.2 Hz, 1524, 1252, 2H), 7.52 (d, J = 8.0 Hz, 1168, 1118 2H), 6.95 (m, 2H), 6.82 (m, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC9 348.11 ([M + H]⁺) 8.71 (s, 1H), 8.20 (s, 3115, 1525, 1H), 7.70 (d, J = 8.0 Hz, 1248, 1174 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.40 (m, 1H), 7.19 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H) DC10 348.11 ([M + H]⁺) 8.75 (s, 1H), 8.20 (s, 3114, 1526, 1H), 7.72 (d, J = 8.4 Hz, 1259, 1238, 2H), 7.6 (d, J = 8.4 Hz, 1193, 1114 2H), 7.20-7.40 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H, ), 4.60 (m, 1H) DC11 75.5-78.5 358.14 ([M + H]⁺) 8.55 (s, 1H), 8.10 (s, 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.01 (s, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.15 (m, 1H), 2.34 (s, 6H) DC12 398.05 ([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3055, 2930, 1H), 7.68 (d, J = 8.4 Hz, 1523, 1250, 2H), 7.53 (m, 4H), 1165 7.2 (s, 1H) 6.62 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.15 (m, 1H) DC13 396.16 ([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3108, 1523, 1H), 7.62 (d, J = 8.4 Hz, 1249, 1166, 2H), 7.55 (m, 4H), 1127 7.25 (m, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC14 398.05 ([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3117, 2925, 1H), 7.62 (d, J = 8.4 Hz, 1526, 1246, 2H), 7.55 (m, 4H), 1172, 1117 7.25 (m, 1H), 6.67 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.00 (m, 1H) DC15 397.95 ([M + H]⁺) 8.58 (s, 1H), 8.10 (s, 3120, 1524, 1H), 7.66 (d, J = 8.0 Hz, 1267, 1176, 2H), 7.52 (m, 3H), 1112 7.40 (d, J = 8.0 Hz, 1H), 7.30 (dd, J = 8.4, 2.9 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC16 466 ([M + H]⁺) 8.61 (s, 1H), 8.13 (s, 1H), 7.92 (s, 1H), 7.86 (s, 2H), 7.70 (d, J = 7.0 Hz, 2H), 7.54 (d, J = 7.0 Hz, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC17 430.06 ([M + H]⁺) 8.58 (s, 1H), 8.1 (s, 1H), 3122, 3076, 7.68 (d, J = 8.4 Hz, 2H), 2929, 1523, 7.54 (d, J = 8.4 Hz, 2H), 1250, 1168, 7.51 (s, 1H), 7.42 (s, 1114 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0, Hz, 1H), 4.98 (m, 1H) DC18 92-95 429.91 ([M + H]⁺) 8.57 (s, 1H), 8.11 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.42 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.10 (m, 1H) DC19 97-99 430.321 ([M + H]⁺) 8.58 (s, 1H), 8.12 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.59 (s, 1H), 7.55 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H) DC20 427.0463 (427.0466) 8.58 (s, 1H), 8.15 (s, 2937, 1524, 1H), 7.70 (d, J = 8.4 Hz, 1482, 1278, 2H), 7.58 (d, J = 8.4 Hz, 1249, 1166, 2H), 7.36 (s, 2H), 1112 6.62 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 3.88 (s, 3H) DC21 412.04 ([M + H]⁺) 8.42 (s, 1H), 7.60 (d, J = 8.0 Hz, 3108, 1572, 2H), 7.50 (d, J = 8.0 Hz, 1531, 1242, 2H), 7.40 (s, 1172, 1104 1H), 7.22 (s, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.5 (s, 3H) DC22 147-149 441.01 ([M − H]⁻) 8.62 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC23 412.05 ([M + H]⁺) 7.95 (s, 1H), 7.35 (d, J = 8.0 Hz, 1112, 799 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.39 (s, 1H), 7.29 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 2.51 (s, 3H) DC24 133-134 440.03 ([M + H]⁺) 8.10 (s, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.42-7.38 (m, 3H), 7.28 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.79 (s, 3H) DC25 442.02 ([M − H]⁻) 7.97 (s, 1H), 7.59 (d, J = 8.0 Hz, 1167, 1114, 2H), 7.53 (d, J = 8.0 Hz, 800 2H), 7.38 (m, 1H), 7.29 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.17 (m, 1H), 2.74 (s, 3H) DC26 464.03 ([M − H]⁻) 8.12 (s, 1H), 7.49 (d, J = 8.0 Hz, 1689, 1253, 2H), 1166, 1114, 7.40-7.37 (m 3H), 7.28 (s, 2H), 979, 964 6.66 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.14 (m, 1H), 3.22 (m, 1H), 1.09-1.16 (m, 4H) DC27 473.94 ([M − H]⁻) 8.19 (s, 1H), 7.64 (d, J = 7.2 Hz, 1571, 1331, 2H), 7.55 (d, 7.2 Hz, 1170, 1113, 2H), 7.39 (s, 1H), 764 7.30 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 8.0, 16.0 Hz, 1H), 4.18 (m, 1H), 3.58 (s, 3H) DC28 421.22 ([M + H]⁺) 8.79 (s, 1H), 8.18 (s, 3126, 2233, 1H), 7.80 (m, 3H), 1516, 1250, 7.52 (m, 2H), 7.24 (m, 1H), 1165, 1109 6.63 (d, J = 16.0 Hz, 1H), 6.54 (d, J = 16.0, 7.6 Hz, 1H), 4.19 (m, 1H) DC29 421.22 ([M + H]⁺) 8.80 (s, 1H), 8.2 (s, 1H), 3005, 1716, 7.75-7.82 (m, 3H), 1363, 1223 7.41 (t, J = 2 Hz, 1H), 7.26 (m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 7.6 Hz, 1H), 4.16 (m, 1H) DC30 489.17 ([M + H]⁺) 8.81 (s, 1H), 8.20 (s, 2964, 2234, 1H), 7.94 (s, 1H), 1289, 1166, 7.85 (m, 3H), 7.79 (m, 2H), 1136 6.70 (d, J = 16.0 Hz, 1H), 6.58 (dd, J = 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC31 117-118 455.27 ([M + H]⁺) 8.80 (s, 1H), 8.20 (s, 1H), 7.82 (m, 3H), 7.4 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC32 388.0705 (388.0703) 8.82 (s, 1H), 8.22 (s, 3126, 2234, 1H), 7.82-7.78 (m, 3H), 1520, 1280, 7.38-7.30 (m, 3H), 1164, 1112 6.62 (d, J = 16.1 Hz, 1H), 6.56 (dd, J = 16.1, 6.8 Hz, 1H), 4.18 (m, 1H) DC33 455.22 ([M − H]⁻) 8.80 (s, 1H), 8.20 (s, 3122, 3086, 1H), 7.82-7.80 (m, 3H), 2234, 1517, 7.70-7.50 (m, 3H), 1327, 1168, 6.65 (d, J = 16.9 Hz, 1H), 1113 6.54 (dd, J = 16.9, 6.8 Hz, 1H), 4.25 (m, 1H) DC34 452.0412 (452.0419) 8.85 (s, 1H), 8.23 (br s, 3122, 2934, 1H), 7.83-7.78 (m, 3H), 2231, 1516, 7.33 (s, 2H), 6.69 (d, J = 14.9 Hz, 1480, 1248, 1H), 6.50 (dd, 1211, 1165, J = 14.9, 7.2 Hz, 1H), 1111 4.15 (m, 1H), 3.90 (s, 3H) DC35 439.01 ([M − H]⁻) 8.60 (s, 1H), 8.20 (s, 2233, 1518, 1H), 7.82 (m, 3H), 1250, 1169, 7.28 (m, 2H), 6.65 (d, J = 16.0 Hz, 1035, 817 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC36 437.25 ([M + H]⁺) 8.70 (s, 1H), 7.80 (m, 2927, 2233, 3H), 7.40 (s, 1H), 1572, 1531, 7.28 (s, 2H), 6.63 (d, J = 16.0 Hz, 1248, 1166, 1H), 6.50 (dd, J = 16.0, 1112 8.0 Hz, 1H), 4.18 (m, 1H), 2.50 (s, 1H) DC37 109-111 466.10 ([M − H]⁻) 8.86 (s, 1H), 7.89 (m, 3H), 7.40 (s, 1H), 7.30 (s, 2H), 6.68 (d, J = 16.0 Hz, 1H), 6.57 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC38 96-98 436.11 ([M − H]⁻) 8.58 (s, 1H), 7.75 (m, 3H), 7.40 (s, 1H), 7.28 (s, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.2 Hz, 1H), 4.40 (br s, 2H), 4.15 (m, 1H) DC39 224-226 480.30 ([M + H]⁺) 8.65 (s, 1H), 8.18 (br s, 3352, 2237, 1H), 7.80-7.70 (m, 3H), 1707, 1163, 7.40 (s, 1H), 7.27 (s, 841 2H), 7.36 (m, 1H), 7.28 (m, 2H), 6.60 (d, J = 16.8 Hz, 1H), 6.47 (m, 1H), 4.16 (m, 1H), 2.40 (br s, 3H) DC40 70-73 436.11 ([M − 2H]⁻) 8.86 (s, 1H), 7.88 (m, 3H), 7.44 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0 7.6 Hz, 1H), 4.19 (m, 1H) DC41 72-75 469.95 ([M − H]⁻) (DMSO-d₆) 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J = 8.4 Hz, 1H), 6.42 (dd, J = 15.6, 9.2 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H) DC42 104-107 609.98 ([M + H]⁺) 8.78 (s, 2H), 7.83 (s, 2234, 1714, 1H), 7.80 (m, 2H), 1114, 807 7.42 (s, 2H), 6.65 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.8 Hz, 1H), 4.17 (m, 1H), 42.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H), DC43 109-112 540.04 ([M + H]⁺) (DMSO-d₆) 10.94 (br s, 3233, 2233, 1H), 8.36 (s, 1H), 1699, 1114, 8.08 (m, J = 8.4 Hz, 1H), 807 7.91 (s, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 15.6, 9.2 Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H) DC44 435.26 [M − H]⁻ 8.33 (s, 1H), 8.23 (s, 2236, 1510, 1H), 7.66 (s, 1H), 1114, 801 7.60 (s, 1H), 7.41 (m, 1H), 7.28 (m, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.20 (s, 3H) DC45 75-78 468.87 [M − H]⁻ 8.36 (s, 1H), 8.23 (s, 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.41 (s, 2H), 6.62 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.6 Hz, 1H), 4.16 (m, 1H), 2.20 (s, 3H) DC46 411.4 ([M]⁺) 8.83 (s, 1H), 8.21 (s, ¹³C NMR (δ)³ 1H), 7.83 (d, J = 8.5 Hz, 155.63, 1H), 7.61 (d, J = 1.9 Hz, 153.27, 1H), 7.52 (dd, J = 8.4, 153.12, 1.9 Hz, 1H), 7.28 (d, J = 3.8 Hz, 143.01, 2H), 6.93 (d, J = 11.5 Hz, 137.89, 1H), 136.25, 6.26-6.20 (m, 1H), 4.22 (m, 134.03, 1H) 133.88, 132.23, 131.23, 131.18, 129.20, 126.17, 125.04, 124.99 DC47 139-141 474.16 ([M − H]⁻) 8.51 (s, 1H), 8.14 (s, 1H), 7.75 (s, 1H), 7.5 (m, 2H), 7.4 (s, 1H), 7.30 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC48 124-126 414.05 [M − H]⁻ 8.69 (s, 1H), 8.14 (s, 1H), 7.96 (d, J = 4.8 Hz, 1H), 7.39-7.27 (m, 5H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC49 81-83 463.96 [M − H]⁻ 8.57 (s, 1H), 8.14 (s, 1H), 7.60 (m, 2H), 7.44 (m, 3H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC50 140-143 430.07 [M − H]⁻) 8.56 (s, 1H), 8.13 (s, 1110, 803 1H), 7.59 (d, J = 1.2 Hz, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC51 118-121 464.22 ([M − H]⁻) 8.32 (s, 1H), 8.15 (s, 1H), 7.82 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.29 (s, 2H), 6.70 (d, J = 15.6 Hz, 1H), 6.50 (dd, J = 15.6, 8.0 Hz, 1H), 4.20 (m, 1H) DC52 9.99 (s, 1H), 8.42 (s, 3123, 3079, 1H), 8.12 (s, 1H), 2925, 1692, 8.01 (s, 1H), 7.68 (m, 1H), 1571, 1512, 7.44 (m, 1H), 7.33 (m, 1253, 1164, 1H), 7.22 (s, 2H), 1111 6.62 (d, J = 16.7 Hz, 1H), 6.45 (dd, J = 16.7, 9.3 Hz, 1H), 4.10 (m, 1H) DC53 8.30 (m, 1H), 8.00 (br s, 3250, 3043, 1H), 7.75 (m, 1H), 1683, 1116 7.68 (m, 1H), 7.55 (m, 1H), 7.36 (m, 1H), 7.28 (m, 2H), 6.70 (m, 1H), 6.58 (br s, 1H), 6.33 (m, 1H), 5.88 (m, 2H), 4.10 (m, 1H) DC54 56-58 441.07 ([M − H]⁻) 8.40 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.4 (s, 1H), 7.29 (m, 2H), 6.69 (d, J = 15.6 Hz, 1H), 6.57 (dd, J = 15.6, 7.8 Hz, 1H), 4.15 (m, 1H) DC55 412.97 ([M + H]⁺) 8.37 (s, 1H), 8.18 (s, 1H), 7.39 (s, 1H), 7.30 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.90 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 8.2 Hz, 1H), 4.20 (m, 1H), 2.50 (br s, 2H) DC56 175-177 453 ([M − H]⁻) 9.59 (br s, 1H), 8.55 (s, 1H), 8.47 (s, 2H), 8.23 (s, 1H), 7.30 (m, 4H), 6.62 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.20 (s, 3H) DC57 426.0627 (426.0626) 8.33 (s, 1H), 8.16 (s, 3342, 3112, 1H), 7.38 (s, 1H), 2931, 1606, 7.29 (s, 2H), 7.15 (d, J = 7.6 Hz, 1583, 1574, 1H), 6.80 (d, J = 7.6 Hz, 1528, 1153 1H), 6.74 (m, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.35 (dd, J = 15.6, 8.4 Hz, 1H), 5.40 (br s, 1H), 4.15 (m, 1H), 2.90 (s, 3H) DC58 94-97 440.0424 (440.0419) (DMSO-d₆) 8.76 (s, 3403, 3304, 1H), 8.16 (s, 1H), 3178, 1674, 7.90 (br s, 1H), 7.83 (s, 1H), 1571, 1169, 7.70 (d, J = 7.9 Hz, 1H), 1108 7.71-7.67 (m, 3H), 7.58 (d, J = 7.9 Hz, 1H), 7.52 (br s, 1H), 7.00 (dd, J = 15.8, 8.7 Hz, 1H), 6.85 (d, J = 15.8 Hz, 1H), 4.85 (m, 1H) DC59 87-90 (DMSO-d₆) 9.00 (s, 1H), 8.63 (s, 1H), 8.17 (s, 1H), 7.70-7.59 (m, 5H), 7.00 (dd, J = 16.2, 9.7 Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 5.90 (br s 2H), 4.83 (m, 1H) DC60 469.0577 (469.0572) 8.32 (s, 1H), 8.10 (s, 2987, 1725, 1H), 7.97 (s, 1H), 1518, 1275, 7.65 (d, J = 8.1 Hz, 1H), 1166, 1113 7.47 (d, J = 8.1 Hz, 1H), 7.40 (m, 1H), 7.28 (s, 2H), 6.62 (d, J = 16.5 Hz, 1H), 6.49 (dd, J = 16.5, 7.7 Hz, 1H), 4.23-4.04 (m, 3H), 1.15 (t, J = 8.0 Hz, 3H) DC61 130-132 442.15 ([M + H]⁺) (DMSO-d₆) 9.90 (s, 1H), 8.17 (s, 1H), 8.15 (m, 1H), 7.90 (m, 1H), 7.71 (m, 2H), 7.67 (m, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.03 (dd, J = 16.5, 8.3 Hz, 1H), 6.62 (d, J = 16.5 Hz, 1H), 4.87 (m, 1H) DC62 412.10 ([M + H]⁺) 8.27 (s, 1H), 8.23 (s, 1513, 1252, 1H), 7.40 (m, 3H), 1166, 1112, 7.30 (m, 3H), 6.64 (d, J = 16.0 Hz, 801 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.19 (m, 1H), 2.21 (s, 3H) DC63 446.01 ([M + H]⁺) 8.26 (s, 1H), 8.12 (s, 2928, 1H), 7.42 (s, 2H), 2525, 1249, 7.18-7.28 (m, 3H), 6.62 (d, J = 15.6 Hz, 1169, 1114, 1H), 809 6.39 (dd, J = 15.6, 9.4 Hz, 1H), 4.10 (m, 1H), 2.25 (s, 3H) DC64 475.03 ([M + H]⁺) 8.84 (d, J = 5.8 Hz, 2H), 1683, 1167, 8.33 (s, 1H), 8.20 (s, 650, 479 1H), 7.75 (m, 1H), 7.60 (d, J = 28.6 Hz, 1H), 7.58-7.48 (m, 3H), 7.42 (m, 1H), 7.28 (s, 2H), 6.71 (d, J = 16.9 Hz, 1H), 6.39 (dd, J = 16.9, 8.2 Hz, 1H), 4.15 (m, 1H) DC65 412.05 ([M + H]⁺) 8.55 (s, 1H), 8.12 (s, 722, 111 1H), 7.55 (m, 3H), 7.39 (m, 1H), 7.30 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.17 (m, 1H), 2.40 (s, 3H) DC66 60-61 468.26 ([M + H]⁺) 8.59 (s, 1H), 8.14 (s, 1H), 7.94 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.43 (s, 2H), 7.23 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC67 133-134 432.30 ([M + H]⁺) 8.59 (s, 1H), 8.12 (s, 800, 114 1H), 7.78 (br s, 1H), 7.71 (m, 1H), 7.62 (m, 1H), 7.39 (s, 1H), 7.32 (s, 2H), 7.03 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 0.21 (m, 1H) DC68 412.03 ([M + H]⁺) 8.71 (s, 1H), 8.18 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.28 (m, 2H), 6.08 (d, J = 16.0 Hz, 1H), 4.26 (m, 1H), 2.05 (s, 3H) DC69 162-168 414.03 ([M + H]⁺) 8.56 (s, 1H), 8.11 (s, 1H), 7.70 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54 (m, 2H), 7.40 (m, 1H), 6.91 (d, J = 16.5 Hz, 1H), 6.66 (d, J = 16.5 Hz, 1H) DC70  99-103 428.05 ([M + H]⁺) 8.58 (s, 1H), 8.13 (s, 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.46 (m, 2H), 7.42 (m, 1H), 6.85 (d, J = 16.2 Hz, 1H), 6.40 (d, J = 16.2 Hz, 1H), 3.42 (s, 3H) ^(a) ¹H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

mp Compound (° C.); IR (cm⁻¹); Number [α]_(D) ²⁵ ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR (δ) F4 642.99 ([M + H]⁺) (300 MHz, DMSO-d₆) 3460, 1677, δ 8.58 (s, 1H), 8.20 (t, J = 6.6 Hz, 1165, 557 1H), 7.98-7.89 (m, 4H), 7.80 (d, J = 8.1 Hz, 1H), 7.04 (dd, J = 15.6, 8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.78 (m, 1H), 3.89-3.82 (m, 2H), 1.40 (s, 6H) F5 640.9 ([M + H]⁺) 7.62 (d, J = 1.7 Hz, 3288, 1644, 1H), 7.53 (d, J = 7.8 Hz, 1162 1H), 7.42-7.29 (m, 3H), 6.91 (t, J = 6.7 Hz, 1H), 6.54 (bs, 1H) 6.53 (d, J = 15.9 Hz, 1H), 6.39 (dd, J = 15.9, 7.8 Hz, 1H), 4.74 (q, J = 7.1 Hz, 1H), 4.10 (m, 1H), 4.05-3.72 (m, 2H), 1.53 (d, J = 7.0 Hz, 3H) F6 640.9 ([M + H]⁺) 7.62 (d, J = 1.6 Hz, 3288, 1645, 1H), 7.53 (d, J = 8.0 Hz, 1164 1H), 7.41 (s, 2H), 7.38 (dd, J = 8.0, 1.7 Hz, 1H), 6.86 (t, J = 6.2 Hz, 1H), 6.57-6.49 (m, 2H), 6.40 (dd, J = 15.9, 7.8 Hz, 1H), 4.74 (m, 1H), 4.15-4.04 (m, 1H), 4.00-3.81 (m, 2H), 1.53 (d, J = 7.1 Hz, 3H) F7 574.92 ([M + H]⁺) (300 MHz, DMSO-d₆) 3412, 1685, δ 8.56 (t, J = 6.3 Hz, 1163, 809 1H), 8.43 (d, J = 4.5 Hz, 1H), 7.89 (s, 2H), 7.44-7.34 (m, 3H), 6.88 (dd, J = 15.6, 8.4 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85-4.79 (m, 1H), 4.49-4.44 (m, 1H), 3.99-3.83 (m, 2H), 2.33 (s, 3H), 1.34 (d, J = 7.2 Hz, 3H) F8 652.95 ([M + H]⁺) (400 MHz, DMSO-d₆) 3291, 1647, δ 8.62 (t, J = 6.0 Hz, 1165, 808, 1H), 8.59 (d, J = 7.6 Hz, 565 1H), 7.92-7.91 (m, 3H), 7.60 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85-4.80 (m, 1H), 4.41-4.36 (m, 1H), 4.05-3.99 (m, 1H), 3.91-3.84 (m, 1H), 1.73-1.63 (m, 2H), 0.99 (t, J = 7.6 Hz, 3H) F8A 650.99 ([M − H]⁻) (300 MHz, DMSO-d₆) 3289, 1646, δ 8.64-8.57 (m, 2H), 1164, 808. 7.92-7.91 (m, 3H), 725, 649 7.60 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.01 (dd, J = 15.6, 9.0 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.86-4.80 (m, 1H), 4.42-4.35 (m, 1H), 4.06-3.84 (m, 2H), 1.76-1.62 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). F9 575.04 ([M + H]⁺) (400 MHz, DMSO-d₆) 3407, 1685, δ 8.56 (t, J = 6.0 Hz, 1161, 808 1H), 8.44 (d, J = 7.2 Hz, 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.41-7.35 (m, 2H), 6.87 (dd, J = 16.0, 9.2 Hz, 1H), 6.74 (d, J = 15.2 Hz, 1H), 4.85-4.80 (m, 1H), 4.48-4.44 (m, 1H), 4.03-3.85 (m, 2H), 2.33 (s, 3H), 1.31 (d, J = 7.2 Hz, 3H) F10 638.84 ([M + H]⁺) (400 MHz, DMSO-d₆) 3415, 1652, δ 8.61 (d, J = 7.2 Hz, 1162, 807, 1H), 8.52 (t, J = 6.0 Hz, 561 1H), 7.88-7.87 (m, 3H), 7.56 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.96 (dd, J = 16.6, 9.2 Hz, 1H), 6.73 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m, 1H), 4.46-4.42 (m, 1H), 4.00-3.81 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) F11 638.90 ([M + H]⁺) (400 MHz, DMSO-d₆) 3415, 1652, δ 8.61 (d, J = 7.2 Hz, 1162, 807, 1H), 8.52 (t, J = 6.0 Hz, 561 1H), 7.88-7.87 (m, 3H), 7.56 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.96 (dd, J = 16.6, 9.2 Hz, 1H), 6.73 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m, 1H), 4.46-4.42 (m, 1H), 4.00-3.81 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) F12 638.90 ([M + H]⁺) (400 MHz, DMSO-d₆) 3418, 1646, δ 8.65 (d, J = 7.2 Hz, 1163, 808, 1H), 8.56 (t, J = 8.0 Hz, 564 1H), 7.92 (s, 1H), 7.91 (s, 2H), 7.60-7.58 (m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 8.0 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.83-4.76 (m, 1H), 4.52-4.45 (m, 1H), 4.06-3.82 (m, 2H), 1.33 (d, J = 8.0 Hz, 3H) F13 638.96 ([M + H]⁺) (400 MHz, DMSO-d₆) 3418, 1646, δ 8.65 (d, J = 7.2 Hz, 1163, 808, 1H), 8.56 (t, J = 8.0 Hz, 564 1H), 7.92 (s, 1H), 7.91 (s, 2H), 7.60-7.58 (m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 8.0 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.83-4.76 (m, 1H), 4.52-4.45 (m, 1H), 4.06-3.82 (m, 2H), 1.33 (d, J = 8.0 Hz, 3H) F14 673.31 ([M + H]⁺) (300 MHz, CDCl₃) δ 3422, 1640, 7.91 (s, 1H), 7.82 (s, 1169, 528 2H), 7.62 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 6.80 (bs, 1H), 6.62 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.73-4.70 (m, 1H), 4.40-4.25 (m, 1H), 3.95-3.92 (m, 2H), 1.56 (d, J = 7.5 Hz, 3H) F15 589.00 ([M + H]⁺) (400 MHz, DMSO-d₆) 3295, 1682, δ 8.58 (t. J = 8.8 Hz, 1164, 80 1H), 8.32 (d, J = 8.0 Hz, 1H), 7.85 (s, 2H), 7.42 (s, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 6.83 (dd, J = 15.6 Hz, 8.8 Hz, 1H), 6.71 (d, J = 15.6 Hz, 1H), 4.77-4.81 (m, 1H), 4.30-4.35 (m, 1H), 3.94-4.00 (m, 1H), 3.80-3.86 (m, 1H), 2.29 (s, 3H), 1.71-1.60 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H) F15A 588.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3290, 1646, δ 8.61 (t, J = 6.0 Hz, 1165, 808. 1H), 8.35 (d, J = 7.5 Hz, 725, 651 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 6.88 (dd, J = 15.9, 8.7 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 4.40-4.32 (m, 1H), 4.04-3.82 (m, 2H), 2.33 (s, 3H), 1.76-1.62 (m, 2H), 0.91 (t, J = 7.5 Hz, 3H) F16 643.06 ([M + H]⁺) (400 MHz, DMSO-d₆) 3292, 1652, δ 8.65-8.60 (m, 2H), 1167, 809 7.95 (s, 1H), 7.89-7.82 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 7.04 (dd, J = 15.6, 9.2 Hz, 1H), 6.85 (d, J = 15.9 Hz, 1H), 4.85-4.80 (m, 1H), 4.38-4.33 (m, 1H), 4.01 (m, 2H), 1.72-1.58 (m, 2H), 0.86 (t, J = 7.6 Hz, 3H) F16A 640.9 ([M − H]⁻) (300 MHz, DMSO-d₆) 3290, 1651, δ 8.66-8.62 (m, 2H), 1166, 809 7.98 (s, 1H), 7.92-7.87 (m, 3H), 7.51 (d, J = 7.8 Hz, 1H), 7.04 (dd, J = 15.6, 9.0 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H), 4.41-4.37 (m, 1H), 4.05-3.87 (m, 2H), 1.72-1.63 (m, 2H), 0.90 (t, J = 6.9 Hz, 3H) F17 628.95 ([M + H]⁺) (400 MHz, DMSO-d₆) 3299, 1686, δ 8.55 (t, J = 6.4 Hz, 1165, 568 1H), 8.42 (d, J = 7.6 Hz, 1H), 7.89 (s, 1H), 7.82 (s, 2H), 7.45 (s, 1H), 7.41-7.35 (m, 2H), 6.85 (dd, J = 16.0 Hz, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.81-4.76 (m, 1H), 4.48-4.44 (m, 1H), 3.99-3.84 (m, 2H), 2.33 (s, 3H), 1.30 (d, J = 7.6 Hz, 3H) F18 629.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3407, 1713, δ 8.76 (d, J = 7.8 Hz, 1160, 807 1H), 8.61 (t, J = 12.9 Hz, 1H), 7.98 (s, 1 H), 7.92-7.88 (m, 3H), 7.56 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 16.2, 9.3 Hz, 1H), 6.89 (d, J = 16.0 Hz, 1H), 4.89-4.83 (m, 1H), 4.51-4.47 (m, 1H), 4.01-3.88 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) F19 692.88 ([M + H]⁺) (400 MHz, DMSO-d₆) 3404, 1646, δ 8.61 (d, J = 7.2 Hz, 1165, 565 1H), 8.52 (t, J = 12.8 Hz, 1H), 7.88 (s, 1H), 7.85 (s, 1H), 7.80 (s, 2H), 7.56 (d, J = 6.8 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.95 (dd, J = 15.6, 9.2 Hz, 1H), 6.72 (d, J = 15.6 Hz, 1H), 4.77-4.72 (m, 1H), 4.46-4.42 (m, 1H), 3.98-3.82 (m, 2H), 1.27 (d, J = 6.8 Hz, 3H) F20 629.29 ([M + H]⁺) (400 MHz, DMSO-d₆) 3407, 1679, δ 8.75 (d, J = 7.8 Hz, 1165, 808 1H), 8.59 (t, J = 6.6 Hz, 1H), 7.98-7.88 (m, 4H), 7.56 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.6, 8.7 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.83 (m, 1H), 4.52-4.47 (m, 1H), 4.01-3.88 (m, 2H), 1.30 (d, J = 6.9 Hz, 3H) F20A [α]_(D) ²⁵ = +49.2 (c, 628.89 ([M + H]⁺) (400 MHz, DMSO-d₆) 3315, 1657, 1% δ 8.74 (d, J = 7.6 Hz, 1167, 700 in 1H), 7.98 (s, 1H), CH₂Cl₂) 7.92-7.89 (m, 3H), 7.56 (d, J = 8.4 Hz, 1H), 7.08 (dd, J = 15.6, 8.8 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.83 (m, 1H), 4.51-4.48 (m, 1H), 3.99-3.86 (m, 2H), 1.49 (d, J = 6.8 Hz, 3H) F20B [α]_(D) ²⁵ = −38.8 (c, 628.89 ([M + H]⁺) (400 MHz, DMSO-d₆) 3315, 1657, 1% in δ 8.74 (d, J = 7.6 Hz, 1167, 700 CH₂Cl₂) 1H), 7.98 (s, 1H), 7.92-7.89 (m, 3H), 7.56 (d, J = 8.4 Hz, 1H), 7.08 (dd, J = 15.6, 8.8 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.83 (m, 1H), 4.51-4.48 (m, 1H), 3.99-3.86 (m, 2H), 1.49 (d, J = 6.8 Hz, 3H) F20C 61-70 629 ([M + H]⁺) 7.64 (t, J = 6.4 Hz, ¹⁹F NMR 1H), 7.52 (d, J = 7.9 Hz, (376 MHz, 1H), 7.42 (s, 1H), CDCl3) δ −59.22, 7.34 (d, J = 2.9 Hz, amide 3H), 6.64 (m, 1H), rotamers −69.43 6.91 (d, J = 11.4 Hz, 1H), and −69.45, 6.19 (dd, J = 11.4, 10.3 Hz, −72.60 1H), 4.94 (p, J = 7.1 Hz, 1H), 4.18 (q, J = 8.8 Hz, 1H), 3.95-3.71 (m, 2H), 1.52 (d, J = 6.9 Hz, 3H) F21 682.98 ([M + H]⁺) (400 MHz, DMSO-d₆) 3302, 1656, δ 8.70 (d, J = 7.2 Hz, 1166, 557 1H), 8.55 (t, J = 6.4 Hz, 1H), 7.94 (s, 1H), 7.87-7.81 (m, 4H), 7.52 (d, J = 8.4 Hz, 1H), 7.04 (dd, J = 15.6, 9.2 Hz, 1H), 6.84 (d, J = 15.6 Hz, 1H), 4.80-4.75 (m, 1H), 4.47-4.44 (m, 1H), 3.97-3.78 (m, 2H), 1.29 (d, J = 7.6 Hz, 3H) F22 605.32 ([M + H]⁺) (300 MHz, DMSO-d₆) 3412, 1645, δ 8.65 (d, J = 7.5 Hz, 1164, 597 1H), 8.55 (t, J = 8.1 Hz, 1H), 7.93-7.87 (m, 3H), 7.78 (d, J = 8.1 Hz, 1H), 7.71-7.66 (m, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 6.0 Hz, 1H), 7.03 (dd, J = 15.6, 9.2 Hz, 1H), 6.79 (d, J = 15.9 Hz, 1H), 4.93-4.86 (m, 1H), 4.50-4.45 (m, 1H), 4.00-3.85 (m, 2H), 1.33 (d, J = 7.2 Hz, 3H) F23 609.00 ([M + H]⁺) 7.66 (d, J = 8.4 Hz, 3291, 1645, 1H), 7.43 (s, 1H), 1165, 749 7.40 (s, 2H), 7.34 (d, J = 7.6 Hz, 1H), 6.79 (s, 1H), 6.73 (s, 1H), 6.56 (d, J = 16.4 Hz, 1H), 6.43 (dd, J = 16.4, 8.0 Hz, 1H), 4.64-4.60 (m, 1H), 4.13-4.06 (m, 1H), 4.00-3.85 (m, 2H), 2.09 (m, 1H), 1.87-1.78 (m, 2H), 1.37 (t, J = 7.2 Hz, 3H) F23A 608.99 ([M + H]⁺) (400 MHz, DMSO-d₆) 3292, 1646, δ 8.63 (t, J = 6.4 Hz, 1165, 808 1H), 8.59 (d, J = 8.0 Hz, 1H), 7.91 (s, 2H), 7.77 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.6, 9.2 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.86-4.81 (m, 1H), 4.42-4.37 (m, 1H), 4.05-3.84 (m, 2H), 1.75-1.61 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H) F24 622.97 ([M + H]⁺) (300 MHz, DMSO-d₆) 3421, 1646, δ 8.65 (d, J = 7.5 Hz, 1168 1H), 8.56 (bs, 1H), 7.92-7.85 (m, 3H), 7.76-7.73 (m, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.04 (dd, J = 15.6, 9.0 Hz, 1H), 6.08 (d, J = 15.9 Hz, 1H), 4.98-4.92 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) F25 594.94 ([M + H]⁺) (300 MHz, DMSO-d₆) 3299, 1687, δ 8.66 (d, J = 7.2 Hz, 1164, 808 1H), 8.57 (t, J = 6.0 Hz, 1H), 7.91 (s, 2H), 7.77 (s, 1H), 7.57 (d, J = 6.9 Hz, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.02 (dd, J = 15.6, 9.0 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.87-4.80 (m, 1H), 4.51-4.47 (m, 1H), 4.04-3.88 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) F26 588.96 ([M − H]⁻) (300 MHz, DMSO-d₆) 3429, 1645, δ 10.54 (bs, 1H), 1165, 750 8.53 (d, J = 6.9 Hz, 1H), 7.89 (s, 2H), 7.45-7.38 (m, 3H), 6.88 (dd, J = 15.9, 8.4 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.87-4.79 (m, 2H), 4.67-4.65 (m, 1H), 4.53-4.50 (m, 1H), 2.33 (s, 3H), 1.37 (d, J = 6.9 Hz, 3H) F27 655.27 ([M + H]⁺) (300 MHz, DMSO-d₆) 3422, 1657, δ 10.52 (bs, 1H), 1161, 806, 8.74 (d, J = 5.7 Hz, 1H), 557 7.93-7.91 (m, 3H), 7.62 (d, J = 8.7 Hz, 1H), 7.48 (d, J = 7.8 Hz, 1H), 6.98 (dd, J = 15.0, 6.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.88-4.80 (m, 2H), 4.52-4.43 (m, 2H), 1.37 (d, J = 6.9 Hz, 3H) F28 644.94 ([M + H]⁺) (300 MHz, DMSO-d₆) 3257, 1663, δ 10.57 (bs, 1H), 1170, 809, 8.85 (d, J = 7.5 Hz, 1H), 552 7.99-7.70 (m, 4H), 7.65 (d, J = 8.1 Hz, 1H), 7.07 (dd, J = 15.9, 6.9 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.88-4.84 (m, 2H), 4.67-4.50 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H) F29 602.94 ([M − H]⁻) (300 MHz, DMSO-d₆) 3420, 1645, δ 9.87 (bs, 1H), 1164, 750 8.40 (bs, 1H), 7.89 (s, 2H), 7.54 (d, J = 8.1 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 7.8 Hz, 1H), 6.88 (dd, J = 15.9, 8.7 Hz, 1H), 6.75 (d, J = 15.3 Hz, 1H), 4.85-4.79 (m, 1H), 4.55-4.50 (m, 2H), 2.32 (s, 3H), 1.60 (s, 6H) F30 611.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3432, 1651, δ 10.65 (bs, 1H), 1259, 750 8.75 (d, J = 6.9 Hz, 1H), 7.90 (s, 2H), 7.78 (s, 1H), 7.58-7.49 (m, 2H), 6.98 (dd, J = 14.7 Hz, 8.0 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.89-4.84 (m, 2H), 4.78-4.60 (m, 1H), 4.59-4.49 (m, 1H), 1.37 (d, J = 6.9 Hz, 3H) F31 618.87 ([M − H]⁻) (300 MHz, DMSO-d₆) 3436, 1261, δ 10.14 (s, 1H), 750 9.72 (broad s, 1H), 7.88 (s, 2H), 7.40-7.34 (m, 2H), 7.24 (d, J = 7.8 Hz, 1H), 6.81 (dd, J = 16.0, 8.0 Hz, 1H) 6.69 (d, J = 16.0 Hz, 1H), 4.84-4.78 (m, 1H), 4.55-4.50 (m, 2H), 2.29 (s, 3H), 1.76 (s, 6H) ^(a1)H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 2B Analytical Data for Compounds in Table 1B. Compound mp IR (cm⁻¹); Number (° C.) ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR (δ) P1 590.91 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3327, 1703, 8.69 (t, J = 5.6 Hz, 1H), 1164, 595 8.56 (t, J = 6.4 Hz, 1H), 7.93-7.88 (m, 3H), 7.77-7.75 (m, 1H), 7.70-7.66 (m, 1H), 7.62-7.60 (m, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 8.8 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.92-4.87 (m, 1H), 3.97-3.90 (m, 4H) P2 581.91 ([M − H]⁻) 7.63-7.62 (m, 1H), 3280, 2243, 7.58 (d, J = 8.4 Hz, 1H), 1637, 1166 7.39-7.37 (m, 1H), 7.12 (d, J = 8.0 Hz, 2H), 6.78 (t, J = 4.8 Hz, 1H), 6.65 (bs, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 15.6, 7.6 Hz, 1H), 4.24-4.20 (m, 3H), 4.00-3.92 (m, 2H) P12 577.07 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3311, 1646, 8.61-8.54 (m, 2H), 1164, 714 7.86 (d, J = 6.4 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.45-7.42 (m, 2H), 6.95 (dd, J = 15.6, 9.6 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.86-4.76 (m, 1H), 3.98-3.89 (m, 4H), 2.43 (s, 3H) P14 638.80 ([M − H]⁻) (300 MHz, DMSO-d₆) δ 3435, 1166, 10.55 (t, J = 6.0 Hz, 749, 597 1H), 10.53 (t, J = 5.2 Hz, 1H), 7.90 (s, 1H), 7.87 (d, J = 8.8 Hz, 2H) 7.59-7.56 (m, 1H), 7.37-7.35 (m, 1H), 6.98 (dd, J = 15.6, 9.0 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.84-4.77 (m, 1H), 4.70-4.58 (m, 4H) P15 590.8 ([M − H]⁻) (400 MHz, DMSO-d₆) δ 3243, 2923, 10.62 (t, J = 6.0 Hz, 1106, 614 1H), 10.54 (t, J = 5.2 Hz, 1H), 7.89 (s, 2H), 7.42 (s, 1H), 7.39-7.37 (m, 1H), 7.24 (d, J = 7.6 Hz, 1H), 6.84 (dd, J = 15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6, 1H), 4.84-4.80 (m, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.65-4.56 (m, 2H), 2.35 (s, 3H) P82 590.9 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3298, 1643, 8.65 (d, J = 7.2 Hz, 1162 1H), 8.56 (t, J = 6.6 Hz, 1H), 7.88 (s, 1H), 7.59-7.56 (m, 2H), 7.47-7.40 (m, 2H), 6.90-6.88 (m, 2H), 4.97-4.94 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) P84 82-85 581.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 8.74 (d, J = 7.2 Hz, 1H), 8.59 (t, J = 6.6 Hz, 1H), 7.96 (s, 1H), 7.89 (d, J = 7.5 Hz, 1H), 7.61-7.44 (m, 3H) 6.99 (m, 2H), 4.98-4.95 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.88 (m, 2H), 1.29 (d, J = 6.8 Hz, 3H) P156 639.0 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3436, 2924, 8.66 (d, J = 8.0 Hz, 1H), 1662, 1162, 8.56 (t, J = 5.6 Hz, 1H), 750 7.95-7.93 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 8.8 Hz, 1H), 6.94 (d, J = 15.6 Hz, 1H), 5.09-5.04 (m, 1H), 4.53-4.43 (m, 1H), 4.02-3.86 (m, 2H), 1.31 (t, J = 6.8 Hz, 3H) P226 620.95 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3413, 1668, 8.65 (d, J = 7.5 Hz 1H), 1161 8.57 (t, J = 6.3 Hz, 1H), 7.90 (s, 1H), 7.60-7.55 (m, 4H), 7.41 (d, J = 7.8 Hz, 2H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H), 6.78 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 4.50-4.43 (m, 1H), 4.00-3.85 (m, 2H), 1.33 (d, J = 7.8 Hz, 3H) P228 610.94 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3413, 1668, 8.74 (d, J = 7.5 Hz, 1H), 1161, 564 8.61 (t, J = 6.6 Hz, 1H), 7.96 (s, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.63-7.53 (m, 4H), 7.41 (d, J = 7.5 Hz, 1H), 7.08 (dd, J = 15.6, 8.7 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.84-4.81 (m, 1H), 4.51-4.43 (m, 1H), 3.99-3.85 (m, 2H), 1.29 (d, J = 7.5 Hz, 3H) P298 634.8 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3307, 2925, 8.65 (d, J = 7.6 Hz, 1H), 1652, 1164 8.55 (t, J = 6.4 Hz, 1H), 7.92-7.91 (d, J = 1.6 Hz, 1H), 7.67 (s, 1H), 7.62-7.58 (m, 2H), 7.54 (d, J = 9.6 Hz, 1H) 7.41 (d, J = 8.0 Hz, 1H), 6.97 (dd, J = 15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.82-4.77 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.82 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H) P300 623.2 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3296, 1652, 8.74 (d, J = 7.6 Hz, 1H), 1167 8.60 (d, J = 16.0 Hz, 1H), 7.97 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.68 (s, 1H), 7.62-7.59 (m, 1H), 7.56-7.53 (m, 2H), 7.06 (dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.84-4.80 (m, 1H), 4.51-4.47 (m, 1H), 4.03-3.85 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P442 584.87 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3410, 1692, 8.64 (d, J = 7.2 Hz, 1H), 1163, 769, 8.57 (t, J = 12.8 Hz, 565 1H), 7.87 (d, J = 1.2 Hz, 1H), 7.58-7.52 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.41-7.37 (m, 2H), 6.90 (dd, J = 16.0, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.68-4.63 (m, 1H), 4.49-4.46 (m, 1H), 3.99-3.86 (m, 2H), 2.35 (s, 3H), 1.28 (d, J = 7.2 Hz, 3H) P444 574.98 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3292, 1661, 8.73 (d, J = 8.0 Hz, 1H), 1158, 741 8.60 (t, J = 6.0 Hz, 1H), 7.92 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.55-7.53 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 6.98 (dd, J = 15.6, 8.8 Hz, 1H), 6.86 (d, J = 15.6 Hz, 1H), 4.70-4.66 (m, 1H), 4.50-4.47 (m, 1H), 3.99-3.82 (m, 2H), 2.35 (s, 3H), 1.27 (d, J = 7.2 Hz, 3H) P514 583.0 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3276, 1638, 8.64 (d, J = 7.2 Hz, 1H), 1167, 598 8.57 (t, J = 6.3 Hz, 1H), 7.86 (s,1H), 7.58 (d, J = 7.5 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.26 (d, J = 6.6 Hz, 2H), 6.88 (dd, J = 15.9, 8.4 Hz, 1H), 6.73 (d, J = 15.9 Hz, 1H), 4.58-4.46 (m, 2H), 4.00-3.85 (m, 2H), 2.24 (s, 6H), 1.31 (d, J = 7.5 Hz, 3H) P516 573.37 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3299, 1654, 8.73 (d, J = 7.8 Hz, 1H), 1165 8.61 (t, J = 6.3 Hz, 1H), 7.88 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 6.9 Hz, 2H), 6.98 (dd, J = 15.6, 8.4 Hz, 1H), 6.85 (d, J = 15.6 Hz, 1H), 4.57-4.46 (m, 2H), 3.99-3.85 (m, 2H), 2.24 (s, 6H), 1.29 (d, J = 7.2 Hz, 3H) P568 692.88 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3306, 1646, 8.65 (d, J = 7.8 Hz, 1H), 1164 8.55 (t, J = 7.8 Hz, 1H), 7.98 (s, 1H), 7.90 (s, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.60-7.57 (m, 1H), 7.51-7.48 (m, 1H), 7.41-7.39 (m, 1H), 6.96 (dd, J = 15.6, 8.7 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.81-4.72 (m, 1H), 4.50-4.46 (m, 1H), 4.01-3.82 (m, 2H), 1.31 (d, J = 6.9 Hz, 3H) P586 646.9 ([M − H]⁻) 7.64 (s, 1H), 3384, 1647, 7.56-7.54 (m, 2H), 7.43-7.39 (m, 1164, 749, 2H), 7.33 (s, 1H), 566 6.81 (bs, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 6.45 (dd, J = 16.0, 7.6 Hz, 1H), 4.75-4.72 (m, 1H), 4.14-4.10 (m, 1H), 4.00-3.90 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P588 638.84 ([M + H]⁺) (300 MHz, CDCl₃) δ 3304, 2928, 7.69 (s, 1H), 1650, 1165, 7.62-7.59 (m, 1H), 7.55-7.49 (m, 673, 558 2H), 7.42 (s, 1H), 7.32 (s, 1H), 6.88 (bs, 1H), 6.65 (d, J = 16.2 Hz, 1H), 6.49 (dd, J = 16.2, 8.1 Hz, 1H), 6.34 (d, J = 7.2 Hz, 1H), 4.76-4.71 (m, 1H), 4.15-4.12 (m, 1H), 3.96-3.89 (m, 2H), 1.49 (d, J = 7.3 Hz, 3H) P660 682.8 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3310, 1650, 8.74 (d, J = 8.0 Hz, 1H), 1166, 558 8.60 (t, J = 8.8 Hz, 1H), 7.99-7.96 (m, 2H), 7.90 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 8.3 Hz, 1H), 7.55-7.50 (m, 2H), 7.04 (dd, J = 15.6, 8.8 Hz, 1H), 6.86 (d, J = 16.0 Hz, 1H), 4.83-4.78 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.86 (m, 2H), 1.29 (d, J = 5.1 Hz, 3H) P730 615.85 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3299, 1651, 8.67 (d, J = 7.8 Hz, 1H), 1166, 739 8.55 (t, J = 6.6 Hz, 1H), 8.31 (s, 1H), 7.90-7.86 (m, 3H), 7.60 (d, J = 9.2 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 6.98 (dd, J = 15.6, 8.7 Hz, 1H), 6.79 (d, J = 15.6 Hz, 1H), 4.96-4.95 (m, 1H), 4.50-4.45 (m, 1H), 3.96-3.88 (m, 2H), 1.31 (d, J = 9.3 Hz, 3H) P732 605.96 ([M + H]⁺) (300 MHz, CDCl₃) δ 3297, 1651, 7.91 (s, 1H), 7.69 (s, 1167, 749 1H), 7.64-7.50 (m, 4H), 6.71 (bs, 1H), 6.67 (d, J = 16.2 Hz, 1H), 6.52 (dd, J = 15.9, 7.8 Hz, 1H), 6.30 (d, J = 6.9 Hz, 1H), 4.73-4.69 (m, 1H), 4.30-4.24 (m, 1H), 3.96-3.91 (m, 2H), 1.49 (d, J = 7.2 Hz, 3H) P802 578.1 ([M − H]⁻) (300 MHz, DMSO-d₆) 3307, 2927, δ 8.65 (d, J = 7.2 Hz, 2238, 1659, 1H), 8.56 (t, J = 6.3 Hz, 1166 1H), 8.20-8.18 (m, 1H), 8.00-7.90 (m, 2H), 7.66-7.54 (m, 2H), 7.42 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.51-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P804 570.3 ([M + H]⁺) (300 MHz, DMSO-d₆) 3301, 3078, δ 8.74 (d, J = 7.8 Hz, 2239, 1657, 1H), 8.59 (t, J = 6.6 Hz, 1167 1H), 8.21-8.19 (m, 1H), 8.01-7.96 (m, 2H), 7.90 (d, J = 8.1 Hz, 1H), 7.66-7.60 (m, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.08 (dd, J = 15.9, 8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.91-4.85 (m, 1H), 4.52-4.47 (m, 1H), 3.99-3.88 (m, 2H), 1.29 (d, J = 6.9 Hz, 3H) P1090 569.89 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3277, 1698, 8.64 (d, J = 7.5 Hz, 1H), 1167, 518 8.55 (t, J = 6.3 Hz, 1H), 7.86 (s, 1H), 7.58 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 6.9 Hz, 1H), 7.41-7.36 (m, 3H), 7.21-7.15 (m, 1H), 6.91 (dd, J = 15.6, 8.7 Hz, 1H), 6.74 (d, J = 15.9 Hz, 1H), 4.66-4.60 (m, 1H), 4.50-4.45 (m, 1H), 4.03-3.85 (m, 2H), 2.26 (s, 3H), 1.31 (d, J = 7.2 Hz, 3H) P1092 559.05 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3437, 1643, 8.74 (d, J = 7.8 Hz, 1H), 1165 8.59 (t, J = 6.3 Hz, 1H), 7.92 (s, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H), 7.42-7.38 (m, 1H), 7.19 (t, J = 9.3 Hz, 1H), 7.00 (dd, J = 15.9, 8.7 Hz, 1H), 6.85 (d, J = 15.9 Hz, 1H), 4.69-4.62 (m, 1H), 4.51-4.47 (m, 1H), 4.02-3.85 (m, 2H), 2.26 (s, 3H), 1.29 (d, J = 7.2 Hz, 3H) P1197 576.83 ([M + H]⁺) (300 MHz, CDCl₃) δ 3311, 1655, 7.62-7.56 (m, 2H), 1166 7.40-7.37 (m, 1H), 7.05-7.00 (m, 2H), 6.72 (bs, 1H), 6.56 (bs, 1H), 6.51 (d, J = 16.2 Hz, 1H), 6.52 (dd, J = 15.9, 7.5 Hz, 1H), 4.21 (d, J = 5.4 Hz, 2H), 4.13-4.08 (m, 1H), 4.02-3.91 (m, 2H) P1269 659.07 ([M + H]⁺) (300 MHz, CDCl₃) δ 3317, 1706, 7.91 (s, 1H), 7.83 (s, 1175, 559 2H), 7.64-7.56 (m, 2H), 7.42-7.39 (m, 1H), 6.74 (bs, 1H), 6.62 (bs, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.50 (dd, J = 15.7, 7.8 Hz, 1H), 4.35-4.30 (m, 1H), 4.21 (d, J = 6.0 Hz, 2H), 4.02-3.90 (m, 2H) P1340 607.00 ([M − H]⁻) (300 MHz, DMSO-d₆) δ 3411, 1652, 8.68 (t, J = 5.7 Hz, 1H), 1166 8.56 (t, J = 6.3 Hz, 1H), 7.93 (s, 1H), 7.87-7.83 (m, 2H), 7.76-7.75 (m, 1H), 7.62-7.55 (m, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.05 (dd, J = 15.6, 9.0 Hz, 1H), 6.88 (d, J = 15.3 Hz, 1H), 4.99-4.92 (m, 1H), 4.01-3.90 (m, 4H) P1411 624.92 ([M + H]⁺) (300 MHz, CDCl₃) δ 3098, 1721, 7.64 (s, 1H), 1214, 723, 7.58-7.55 (m, 3H), 7.51 (s, 1H), 513 7.41-7.38 (m, 1H), 6.77 (bs, 1H), 6.72 (bs, 1H), 6.59 (d, J = 15.9 Hz, 1H), 6.48 (dd, J = 15.9, 7.5 Hz, 1H), 4.24-4.19 (m, 4H), 4.01-3.90 (m, 1H) P1483 608.78 ([M + H]⁺) (300 MHz, CDCl₃) δ 3300, 1657, 7.62-7.54 (m, 3H), 1164, 560 7.39 (d, J = 8.1 Hz, 1H), 7.29-7.24 (m, 1H), 6.84-6.82 (m, 1H), 6.56 (d, J = 15.6 Hz, 1H), 6.49 (dd, J = 15.6, 6.6 Hz, 1H), 4.23-4.19 (m, 2H), 4.01-3.93 (m, 3H) P1556 614.84 ([M + H]⁺) 7.70 (s, 1H), 3369, 1719, 7.63-7.61 (m, 1H), 7.56-7.51 (m, 1164, 807. 1H), 7.41 (s, 2H), 6.65 (d, J = 15.6 Hz, 1H), 6.60 (bs, 2H), 6.50 (dd, J = 15.2, 6.8 Hz, 1H), 4.19-4.13 (m, 3H), 3.98-3.94 (m, 2H) P1558 595.00 ([M − H]⁻) (300 MHz, CDCl₃) δ 3351, 1660, 8.89 (bs, 1H), 1161, 700 7.72-7.69 (d, J = 8.1 Hz, 1H), 7.45-7.35 (m, 4H), 7.25-7.19 (m, 1H), 6.58 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8 Hz, 1H), 4.57 (d, J = 5.7 Hz, 2H), 4.49-4.38 (m, 2H), 4.16-4.03 (m, 1H) P1559 628.95 ([M − H]⁻) (300 MHz, DMSO-d₆) δ 3398, 1664, 10.45 (t, J = 6.4 Hz, 1163, 808 1H), 8.97 (t, J = 6.0 Hz, 1H), 8.02-7.92 (m, 4H), 7.77 (d, J = 7.5 Hz, 1H), 7.10 (dd, J = 15.6, 9.0 Hz, 1H), 6.90 (d, J = 15.6 Hz, 1H), 4.90-4.82 (m, 1H), 4.63-4.58 (m, 2H), 4.23 (d, J = 6.0 Hz, 2H) P1560 574.88 ([M − H]⁻) (400 MHz, DMSO-d₆) δ 3246, 1646, 10.38 (t, J = 6.0 Hz, 1161, 808 1H), 8.65 (t, J = 5.6 Hz, 1H), 7.88 (s, 2H), 7.50-7.42 (m, 3H), 6.88 (dd, J = 15.6, 8.8 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85-4.81 (m, 1H), 4.63-4.54 (m, 2H), 4.24 (d, J = 6.2 Hz, 2H), 2.36 (s, 3H) P1564 576.6 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3351, 1684, 10.48 (t, J = 6.0 Hz, 1163, 808 1H), 8.74 (t, J = 6.2 Hz, 1H), 7.89 (s, 2H), 7.41-7.36 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 15.6, 8.8 Hz, 1H), 6.73 (d, J = 15.6 Hz, 1H), 4.84-4.79 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 3.98-3.92 (m, 2H), 2.32 (s, 3H) P1566 597.00 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3323, 1654, 8.74 (t, J = 5.6 Hz, 1H), 1115, 808 8.30 (t, J = 6.0 Hz, 1H), 8.03-7.84 (m, 4H), 7.61 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 15.6, 8.8 Hz, 1H), 6.89 (d, J = 16.4 Hz, 1H), 4.88-4.81 (m, 1H), 3.89 (d, J = 5.6 Hz, 2H), 3.59-3.48 (m, 3H) P1589 638.9 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3412, 1657, 8.63 (t, J = 5.7 Hz, 1H), 1169, 749, 8.50 (d, J = 9.0 Hz, 1H), 565 7.93-7.91 (m, 3H), 7.62-7.60 (m, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.01 (dd, J = 15.6, 9.6 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.88-4.80 (m, 1H), 4.66-4.60 (m, 1H), 4.00-3.97 (m, 1H), 3.87-3.80 (m, 1H), 1.27 (d, J = 6.9 Hz, 3H) P1591 628.95 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3436, 1667, 8.74 (t, J = 6.0 Hz, 1H), 1261, 749 8.51 (d, J = 8.7 Hz, 1H), 7.99 (s, 1H), 7.92-7.90 (m, 3H), 7.58 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 15.6, 8.7 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.86 (m, 1H), 4.66-4.58 (m, 1H), 4.00-3.92 (m, 1H), 3.88-3.80 (m, 1H), 1.27 (d, J = 7.2 Hz, 3H) P1592 574.98 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3418, 1651, 8.51 (d, J = 8.7 Hz, 1H), 1163, 748 8.41 (t, J = 6.0 Hz, 1H), 7.89 (s, 2H), 7.45-7.35 (m, 3H), 6.83 (dd, J = 15.6, 8.5 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H), 4.65-4.60 (m, 1H), 3.98-3.91 (m, 1H), 3.85-3.78 (m, 1H), 2.36 (s, 3H), 1.26 (d, J = 6.9 Hz, 3H) P1599 689.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3415, 1599, δ 8.67 (bs, 1H), 8.60 (t, 1162, 748 J = 6.0 Hz, 1H), 7.95 (d, J = 9.9 Hz, 2H), 7.91 (s, 1H), 7.78 (d, J = 6.6 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H) 7.12 (dd, J = 15.6, 9.9 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.94-4.91 (m, 1H), 4.52-4.45 (m, 1H), 4.00-3.85 (m, 2H), 1.33 (d, J = 6.9 Hz, 3H) P1601 678.6 ([M + H]⁺) (300 MHz, DMSO-d₆) 3423, 1646, δ 8.73 (bs, 1H), 8.59 (t, 1141, 807 J = 6.0 Hz, 1H), 7.95 (d, J = 9.9 Hz, 2H), 7.88-7.83 (m, 2H), 7.56 (d, J = 7.2 Hz, 1H), 7.12 (dd, J = 15.6, 10.5 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.94-4.91 (m, 1H), 4.51-4.43 (m, 1H), 3.99-3.88 (m, 2H), 1.31 (d, J = 6.9 Hz, 3H) P1603 113-117 563 ([M + H]⁺) 7.80-7.72 (m, 2H), ¹⁹F NMR 7.48-7.44 (m, 2H), (376 MHz, 7.42 (s, 2H), 6.92 (t, J = 6.4 Hz, CDCl₃) δ −68.66, 1H), 6.62 (m, −72.52 1H), 6.42 (dd, J = 15.9, 8.0 Hz, 1H), 4.75 (p, J = 7.1 Hz, 1H), 4.11 (p, J = 8.5 Hz, 1H), 4.07-3.79 (m, 2H), 1.54 (d, J = 7.0 Hz, 3H) P1611A 621.0 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3410, 2925, 8.60 (d, J = 7.8 Hz, 1H), 1645, 1115, 8.28 (t, J = 5.7 Hz, 1H), 748, 561 7.91 (s, 3H), 7.61-7.58 (m, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.01 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.86-4.79 (m, 1H), 4.49-4.44 (m, 1H), 3.55-3.31 (m, 2H), 1.30 (d, J = 6.9 Hz, 3H) P1613A 611.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3297, 1651, 8.70 (d, J = 7.8 Hz, 1H), 1115, 808 8.31 (t, J = 5.7 Hz, 1H), 7.98 (s, 1H), 7.92-7.88 (m, 3H), 7.57-7.55 (m, 1H),), 7.09 (dd, J = 15.3, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.82 (m, 1H), 4.52-4.43 (m, 1H), 3.57-3.47 (m, 2H), 1.29 (d, J = 7.5 Hz, 3H) P1616 602.8 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3305, 1650, 8.64 (d, J = 7.5 Hz, 1H), 1169, 749, 8.11 (t, J = 5.4 Hz, 1H), 559 7.91 (s, 3H), 7.60-7.58 (m, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.00 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.86-4.53 (m, 1H), 4.51-4.42 (m, 2H), 4.35 (t, J = 5.1 Hz, 1H), 3.45-3.31 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H) P1616A 602.8 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3407, 1651, 8.53 (d, J = 7.60 Hz, 1169, 744, 1H), 8.08 (t, J = 6.0 Hz, 559 1H), 7.91-7.90 (m 3H), 7.59 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 9.2 Hz, 1H), 6.77 (d, J = 16.0 Hz, 1H), 4.84-4.80 (m, 1H), 4.50-4.36 (m, 3H), 3.44-3.24 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P1618A 593.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3411, 1651, 8.64 (d, J = 7.8 Hz, 1H), 1115, 809 8.17 (t, J = 5.4 Hz, 1H), 8.03-7.87 (m, 3H), 7.60 (d, J = 7.8 Hz, 1H), 7.09 (dd, J = 15.9, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.53 (m, 1H), 4.53-4.42 (m, 2H), 4.35 (t, J = 5.1 Hz, 1H), 3.44-3.42 (m, 2H), 1.28 (d, J = 6.9 Hz, 3H) P1621 585.0 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3411, 1649, 8.50 (bs, 1H), 7.91 (s, 1168, 806, 3H), 7.83-7.81 (m, 559 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.43. (d, J = 8.1 Hz, 1H), 7.00 (dd, J = 15.9, 9.9 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.86-4.80 (m, 1H), 4.40-4.36 (m, 1H), 3.14-3.06 (m, 2H), 1.28 (d, J = 6.9 Hz, 3H), 1.03 (t, J = 6.0 Hz, 3H) P1623 575.1 ([M + H]⁺) (300 MHz, DMSO-d₆) 3412, 1645, δ 8.59 (bs, 1H), 7.97 (s, 1115, 749 1H), 7.92-7.85 (m, 4H), 7.57 (d, J = 7.8 Hz, 1H), 7.09 (dd, J = 16.2, 9.3 Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 4.89-4.82 (m, 1H), 4.43-4.36 (m, 1H), 3.12-3.05 (m, 2H), 1.26 (d, J = 7.2 Hz, 3H), 1.05 (t, J = 7.5 Hz, 3H) P1624 521.2 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3307, 1642, 8.26 (bs, 1H), 7.89 (s, 1114, 749 1H), 7.85-7.81 (m, 2H), 7.47-7.37 (m, 2H), 7.34 (d, J = 7.5 Hz, 1H), 6.88 (dd, J = 15.9, 8.7 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 4.39-4.34 (m, 1H), 3.13-3.04 (m, 2H), 2.48 (s, 3H), 1.28 (d, J = 7.5 Hz, 3H), 1.04 (t, J = 7.5 Hz, 3H) P1631A 652.8 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3297, 1646, 8.54 (d, J = 7.60 Hz, 1161, 742, 1H), 8.07 (t, J = 5.4 Hz, 555 1H), 7.91-7.90 (m 3H), 7.60 (d, J = 9.2 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 9.0 Hz, 1H), 6.77 (d, J = 16.0 Hz, 1H), 4.85-4.80 (m, 1H), 4.41-4.37 (m, 1H), 3.40-3.26 (m, 2H), 2.50-2.38 (m, 2H), 1.28 (d, J = 7.6 Hz, 3H) P1633A 640.7 ([M − H]⁻) (300 MHz, DMSO-d₆) δ 3299, 1651, 8.66 (d, J = 7.2 Hz, 1H), 1139, 808 8.13 (t, J = 5.4 Hz, 1H), 7.97 (s, 1H), 7.92-7.88 (m, 3H), 7.58 (d, J = 8.2 Hz, 1H), 7.09 (dd, J = 16.3, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89-4.82 (m, 1H), 4.42-4.37 (m, 1H), 3.38-3.24 (m, 2H), 2.44-2.36 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) P1636 176-184 575 ([M − H]⁻) 7.76-7.72 (m, 2H), ¹⁹F NMR 7.48-7.44 (m, 2H), (376 MHz, 7.42 (s, 2H), 6.62 (d, J = 15.9 Hz, CDCl₃) 1H), 6.54 (s, rotomers δ −68.65, 1H), 6.42 (dd, J = 15.9, −72.57, 7.9 Hz, 1H), 4.89 (s, −73.24 1H), 4.11 (p, J = 8.7 Hz, 1H), 3.92 (dqd, J = 22.9, 9.0, 6.5 Hz, 2H), 1.71 (s, 6H) P1638 638.64 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3427, 2924, 8.60 (bs, 1H), 8.44 (t, J = 6.0 Hz, 1651, 1162, 1H), 7.90 (s, 680 3H), 7.59 (d, J = 6.9 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 16.2, 9.6 Hz, 1H), 6.76 (d, J = 15.3 Hz, 1H), 4.88-4.4.80 (m, 1H), 3.92-3.87 (m, 2H), 3.42-3.40 (m, 2H), 2.50-2.49 (m, 2H) P1640 628.9 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3445, 1644, 8.61 (bs, 1H), 8.53 (t, J = 6.0 Hz, 1163, 749 1H), 7.96 (s, 1H), 7.92-7.86 (m, 3H), 7.47 (d, J = 9.0 Hz, 1H), 7.18 (dd, J = 15.6, 8.1 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.91-4.78 (m, 1H), 3.96-3.84 (m, 2H), 3.45-3.38 (m, 2H), 2.50-2.43 (m, 2H) P1641 574.8 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3427, 2926, 8.61 (bs, 1H), 8.27 (t, J = 5.4 Hz, 1645, 1162, 1H), 7.89 (s, 809 2H), 7.47-7.37 (m, 2H), 7.28 (d, J = 8.1 Hz, 1H), 6.88 (dd, J = 15.6, 9.0 Hz, 1H), 6.74 (d, J = 15.9 Hz, 1H), 4.88-4.81 (m, 1H), 3.92-3.86 (m, 2H), 3.45-3.38 (m, 2H), 2.51-2.44 (m, 2H), 2.32 (s, 3H) P1691 654.8 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3301, 1647, 8.64 (d, J = 7.2 Hz, 1H), 1164, 746 8.57 (t, J = 6.3 Hz, 1H), 7.91 (s, 1H), 7.71 (s, 2H), 7.66 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.91-4.71 (m, 1H), 4.50-4.45 (m, 1H), 4.02-3.82 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P1693 645.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3309, 1650, 8.73 (d, J = 7.2 Hz, 1H), 1165, 677 8.61 (d, J = 6.3 Hz, 1H), 7.96 (s, 1H), 7.86-7.80 (m, 1H), 7.71 (s, 2H), 7.67 (d, J = 8.1 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.6, 9.3 Hz, 1H), 6.90 (d, J = 15.9 Hz, 1H), 4.92-4.71 (m, 1H), 4.51-4.49 (m, 1H), 3.99-3.85 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P1696 604.2 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3418, 1645, 8.65 (d, J = 7.2 Hz, 1H), 1165, 750, 8.55 (t, J = 6.0 Hz, 1H), 562 7.92 (d, J = 1.5 Hz, 1H), 7.68 (t, J = 3.3 Hz, 3H), 7.60 (d, J = 6.9 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.3, 8.7 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.83 (t, J = 7.2 Hz, 1H), 4.51 (t, J = 7.2 Hz, 1H), 4.01-3.88 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P1698 595.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3294, 2928, 8.74 (d J = 7.5 Hz, 1H), 1646, 1166, 8.59 (t, J = 6.6 Hz, 1H), 750 7.98 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.69-7.62 (m, 2H), 7.56 (d, J = 7.5 Hz, 1H), 7.09 (dd, J = 15.3, 8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.83-4.80 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.86 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P1776 593.2 ([M + H]⁺) (400 MHz, DMSO-d₆) δ ¹⁹F NMR 8.69 (t, J = 6.0 Hz, 1H), (376 MHz, 8.57 (t, J = 6.4 Hz, 1H), DMSO-d₆) δ −67.98, 7.90 (dd, J = 13.3, 1.8 Hz, −70.71 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.58 (ddd, J = 18.0, 8.2, 1.8 Hz, 2H), 7.44 (d, J = 7.9 Hz, 1H), 6.94 (dd, J = 15.7, 9.0 Hz, 1H), 6.74 (d, J = 15.7 Hz, 1H), 4.81 (p, J = 9.4 Hz, 1H), 4.02-3.87 (m, 4H) P1781 513.2 ([M + H]⁺) 7.85-7.74 (m, 2H), ¹⁹F NMR 7.53-7.41 (m, 4H), (376 MHz, 7.30 (t, J = 6.2 Hz, 1H), CDCl₃) δ −68.78, 7.23 (dd, J = 8.4, 2.0 Hz, −72.44 1H), 7.19 (t, J = 5.2 Hz, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.46 (dd, J = 15.9, 7.8 Hz, 1H), 4.26 (d, J = 5.1 Hz, 2H), 4.21-4.07 (m, 1H), 3.95 (qd, J = 9.1, 6.4 Hz, 2H) P1806 605.0 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3411, 2925, 8.67 (d, J = 7.2 Hz, 1H), 1650, 1163, 8.57 (t, J = 6.3 Hz, 1H), 747 7.91-7.88 (m, 2H), 7.74 (d, J = 8.7 Hz, 1H), 7.64-7.59 (m, 2H), 7.41 (d, J = 8.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.83-4.77 (m, 1H), 4.52-4.43 (m, 1H), 4.05-3.83 (m, 2H), 1.30 (d, J = 7.2 Hz, 3H) P1808 695.1 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3297, 1652, 8.74 (d, J = 7.2 Hz, 1H), 1165, 745 8.59 (s, 1H), 7.96-7.89 (m, 3H), 7.73 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 8.8 Hz, 2H), 7.05 (dd, J = 16.0, 8.8 Hz, 1H), 6.87 (d, J = 16.0 Hz, 1H), 4.85-4.80 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.88 (m, 2H), 1.28 (d, J = 6.8 Hz, 3H) P1862 598.89 ([M + H]⁺) 7.70 (s, 1H), 3324, 1673, 7.62-7.60 (m, 1H), 7.55-7.53 (m, 1164, 772 1H), 7.35 (d, J = 5.6 Hz, 2H), 7.89 (t, J = 6.0 Hz, 1H), 6.67 (t, J = 5.6 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.48 (dd, J = 16.4, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.17-4.08 (m, 1H), 3.97-3.89 (m, 2H) P1864 622.88 ([M − H]⁻) (400 MHz, DMSO-d₆) δ 3256, 1657, 10.39 (bs, 1H), 8.85 (t, J = 6.0 Hz, 1166, 749, 1H), 7.94 (s, 591 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.6, 8.8 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.81-4.79 (m, 1H), 4.63-4.59 (m, 2H), 4.24 (d, J = 6.0 Hz, 2H) P1866 614.91 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3447, 1655, 10.43 (bs, 1H), 8.96 (t, J = 6.0 Hz, 1167, 816 1H), 8.00 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 6.4 Hz, 2H), 7.76 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J = 16.0 Hz, 1H), 4.86-4.78 (m, 1H), 4.62-4.58 (m, 2H), 4.23 (d, J = 5.6 Hz, 2H) P1969 678.77 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3296, 1697, 8.65 (t, J = 5.4 Hz, 1H), 1164, 596 8.54 (t, J = 6.3 Hz, 1H), 7.90-7.86 (m, 2H), 7.82 (s, 2H), 7.60 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 7.8 Hz, 1H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.83-4.76 (m, 1H), 4.01-3.91 (m, 4H) P1970 634.87 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3299, 1658, 8.68 (t, J = 6.0 Hz, 1H), 1164, 745, 8.57 (t, J = 6.0 Hz, 1H), 543 7.89-7.78 (m, 4H), 7.59-7.56 (m, 1H), 7.49-7.46 (m, 1H), 7.02 (dd, J = 15.9, 8.1 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.83-4.76 (m, 1H), 4.01-3.91 (m, 4H) P1971 668.87 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3351, 1705, 8.77 (t, J = 6.0 Hz, 1H), 1165, 551 8.59 (t, J = 6.3 Hz, 1H), 7.99 (s, 1H), 7.93-7.85 (m, 4H), 7.60 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.85-4.79 (m, 1H), 3.98-3.90 (m, 4H) P1972 614.84 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3311, 1650, 8.57 (t, J = 6.4 Hz, 1H), 1163, 543 8.47 (t, J = 6.0 Hz, 1H), 7.88-7.80 (m, 3H), 7.45 (s, 1H), 7.43-7.37 (m, 2H), 6.86 (dd, J = 15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.83-4.74 (m, 1H), 3.98-3.88 (m, 4H), 2.37 (s, 3H) P2009 692.88 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3402, 1659, 8.62 (t, J = 5.7 Hz, 1H), 1165, 560 8.50 (d, J = 8.7 Hz, 1H), 7.93-7.92 (m, 1H), 7.89-7.88 (m, 1H), 7.84 (s, 2H), 7.62-7.59 (m, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.01 (dd, J = 15.9, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.82-4.76 (m, 1H), 4.65-4.58 (m, 1H), 4.00-3.92 (m, 1H), 3.87-3.80 (m, 1H), 1.27 (d, J = 6.9 Hz, 3H) P2010 646.84 ([M − H]⁻) (300 MHz, DMSO-d₆) δ 3406, 1658, 8.63 (t, J = 6.0 Hz, 1H), 1165, 746, 8.50 (d, J = 8.7 Hz, 1H), 583 7.89-7.88 (m, 1H), 7.84 (s, 2H), 7.78 (s, 1H), 7.59-7.56 (m, 1H), 7.46 (d, J = 7.5 Hz, 1H), 7.00 (dd, J = 15.6, 9.0 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.79-4.76 (m, 1H), 4.63-4.60 (m, 1H), 3.95-3.86 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H) P2011 682.93 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3417, 1666, 8.73 (t, J = 5.6 Hz, 1H), 1115, 558 8.50 (d, J = 8.8 Hz, 1H), 7.98 (s, 1H), 7.90-7.89 (m, 2H), 7.85 (s, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 15.6, 9.2 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.84-4.79 (m, 1H), 4.65-4.59 (m, 1H), 4.03-3.95 (m, 1H), 3.87-3.81 (m, 1H), 1.25 (d, J = 6.0 Hz, 3H) P2012 628.89 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3406, 1643, 8.51 (d, J = 8.7 Hz, 1H), 1163, 583 8.41 (t, J = 6.0 Hz, 1H), 7.88 (s, 1H), 7.82 (s, 1H), 7.45-7.34 (m, 3H), 6.87 (dd, J = 15.9, 8.7 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.82-4.75 (m, 1H), 4.65-4.57 (m, 1H), 3.98-3.78 (m, 2H), 2.36 (s, 3H), 1.26 (d, J = 7.2 Hz, 3H) P2036 674.7 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3296, 1651, 8.61 (d, J = 7.8 Hz, 1H), 1113, 534 8.26 (t, J = 5.7 Hz, 1H), 7.92-7.88 (m, 2H), 7.84 (s, 2H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 6.20-5.80 (m, 1H), 4.83-4.74 (m, 1H), 4.51-4.42 (m, 1H), 3.61-3.31 (m, 2H), 1.31 (d, J = 7.5 Hz, 3H) P2038 662.7 ([M − H]⁺) (300 MHz, DMSO-d₆) δ 3292, 1650, 8.69 (d, J = 7.2 Hz, 1H), 1115, 747, 8.30 (bs, 1H), 7.98 (s, 681 1H), 7.89-7.85 (m, 4H), 7.57 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.09 (dd, J = 15.9, 9.6 Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 6.18-5.81 (m, 1H), 4.84-4.78 (m, 1H), 4.50-4.45 (m, 1H), 3.50-3.45 (m, 2H), 1.29 (d, J = 7.2 Hz, 3H) P2041 656.6 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 3305, 1645, 8.56 (d, J = 7.2 Hz, 1H), 1167, 559 8.10 (t, J = 5.2 Hz, 1H), 7.92-7.88 (m, 2H), 7.84 (s, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0, 9.6 Hz, 1H), 6.76 (d, J = 16.0 Hz, 1H), 4.81-4.74 (m, 1H), 4.50-4.36 (m, 3H), 3.56-3.36 (m, 2H), 1.29 (d, J = 6.8 Hz, 3H) P2043 646.9 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3291, 1651, 8.64 (d, J = 7.8 Hz, 1H), 1115, 588 8.15 (t, J = 5.7 Hz, 1H), 7.97 (s, 1H) 7.90-7.85 (m, 4H), 7.57 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 15.9, 9.3 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.84-4.78 (m, 1H), 4.51-4.42 (m, 2H), 4.37-4.33 (m, 1H), 3.45-3.42 (m, 2H), 1.28 (d, J = 7.8 Hz, 3H) P2056 91-94 706.8 ([M + H]⁺) (400 MHz, DMSO-d₆) δ 8.57 (d, J = 7.2 Hz, 1H), 8.09 (t, J = 5.2 Hz, 1H), 7.92-7.88 (m, 2H), 7.84 (s, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 9.1 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.81-4.77 (m, 1H), 4.40-4.36 (m, 1H), 3.40-3.25 (m, 2H) 2.44-2.32 (m, 2H), 1.28 (d, J = 6.8 Hz, 3H) P2058 696.8 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3309, 1650, 8.66 (s, 1H), 8.14 (s, 1141 2H), 7.97 (s, 1H), 7.89-7.85 (m, 3H) 7.57 (d, J = 8.1 1H), 7.06 (dd, J = 16.2, 9.0 Hz, 1H), 6.88 (d, J = 16.2 Hz, 1H), 4.82-4.81 (m, 1H), 4.41-4.37 (m, 1H) 3.38-2.99 (m, 2H), 2.44-2.36 (m, 2H) 1.27 (d, J = 7.2 Hz, 3H) ^(a1)H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 2C Analytical Data for Compounds in Table 1C. Compound IR (cm⁻¹); Number mp (° C.) ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR (δ) FA1 562.89 ([M + H]⁺) (400 MHz, DMSO-d₆) 3418, 1658, δ 8.65 (t, J = 5.2 Hz, 1114, 749 1H), 8.28 (t, J = 6.0 Hz, 1H), 7.91 (s, 2H), 7.78 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.01 (dd, J = 15.6, 9.2 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H), 3.90 (d, J = 6.0 Hz, 2H), 3.59-3.48 (m, 3H) FA2 542.93 ([M + H]⁺) (400 MHz, DMSO-d₆) 3430, 1646, δ 8.45 (t, J = 6.0 Hz, 1113, 749 1H), 8.29 (t, J = 4.5 Hz, 1H), 7.89 (s, 2H), 7.45-7.34 (m, 3H), 6.87 (dd, J = 15.7, 6.9 Hz, 1H), 6.75 (d, J = 15.8 Hz, 1H), 4.85-4.80 (m, 1H), 3.87 (d, J = 4.8 Hz, 2H), 3.57-3.47 (m, 3H), 2.42 (s, 3H) FA3 606.78 ([M + H]⁺) (400 MHz, DMSO-d₆) 3420, 1654, δ 8.65 (t, J = 5.6 Hz, 114, 749, 558 1H), 8.27 (t, J = 5.6 Hz, 1H), 7.93-7.91 (m, 2H), 7.62-7.58 (m, 2H), 7.46 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 15.2, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85-4.81 (m, 1H), 3.89 (d, J = 6.0 Hz, 1H), 3.59-3.48 (m, 2H), 3.17-3.08 (m, 2H) FA4 599.00 ([M + H]⁺) (400 MHz, CDCl₃) δ 9.81 (s, 1H), 8.06 (d, J = 7.1 Hz, 1H), 7.70 (d, J = 5.5 Hz, 1H), 7.44 (s, 1H), 7.37 (t, J = 2.7 Hz, 2H), 7.20 (s, 1H), 6.82 (d, J = 15.9 Hz, 1H), 6.50 (dd, J = 16.0, 8.5 Hz, 1H), 4.14 (m, 3H), 3.89 (m, 2H) FA5 613.10 ([M + H]⁺) (400 MHz, CDCl₃) δ 7.45 (s, 1H), 7.41 (s, 2H), 7.29 (s, 1H), 7.28 (s, 1H), 6.84 (m, 2H), 6.43 (dd, J = 16.0, 8.3 Hz, 1H), 4.25 (d, J = 5.4 Hz, 2H), 4.10 (m, 1H), 3.97 (qd, J = 9.0, 6.4 Hz, 2H), 3.87 (s, 3H) FA6 545.92 ([M + H]⁺) (400 MHz, DMSO-d₆) 3369, 1694, δ 8.56 (t, J = 6.4 Hz, 1164, 713 1H), 8.51 (t, J = 5.6 Hz, 1H), 7.82 (d, J = 6.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.75 (s, 1H), 6.72 (dd, J = 15.6, 6.8 Hz, 1H), 6.62 (d, J = 15.6 Hz, 1H), 6.51 (bs, 2H), 4.82-4.78 (m, 1H), 3.96-3.85 (m, 4H) FA7 638.78 ([M + H]⁺) (300 MHz, CDCl₃) δ 3284, 1667, 7.62-7.56 (m, 2H), 1166, 744, 7.46-7.37 (m, 2H), 591 6.77-6.76 (m, 1H), 6.56 (d, J = 14.1 Hz, 1H), 6.43 (dd, J = 15.9, 7.8 Hz, 1H), 4.14-4.07 (m, 3H), 3.61-3.54 (m, 2H), 2.42-2.34 (m, 2H) FA8 588.87 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 3297, 1658, 8.68 (t, J = 5.7 Hz, 1H), 1165 8.56 (t, J = 6.6 Hz, 1H), 7.91 (s, 1H), 7.61-7.58 (m, 1H), 7.45-7.39 (m, 3H), 6.95 (dd, J = 15.9, 9.3 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.76-4.64 (m, 1H), 4.06-3.92 (m, 4H), 3.90 (s, 3H) FA9 624.92 ([M + H]⁺) (300 MHz, DMSO-d₆) 3430, 1651, δ 9.81 (bs, 1H), 8.69 (s, 1166, 750 1H), 7.90 (s, 2H), 7.78 (s, 1H), 7.59-7.58 (m, 2H), 7.02 (dd, J = 15.8, 9.3 Hz, 1H), 6.78 (d, J = 15.8 Hz, 1H), 4.86-4.79 (m, 1H), 4.57-4.52 (m, 2H), 1.60 (s, 6H) FA10 640.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3434, 1260, δ 10.41 (s, 1H), 750 9.68 (bs, 1H), 7.90 (s, 2H), 7.76-7.67 (m, 1H), 7.53 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 6.97 (dd, J = 15.6, 8.7 Hz, 1H), 6.77 (d, J = 15.6, 1H), 4.86 (t, J = 9.3 Hz, 1H), 4.55-4.47 (m, 2H), 1.75 (s, 6H) FA11 668.8 ([M + H]⁺) (300 MHz, DMSO-d₆) 3425, 1651, δ 9.80 (bs, 1H), 8.69 (s, 1261, 750 1H), 7.92-7.90 (m, 3H), 7.60-7.55 (m, 2H), 7.01 (dd, J = 15.5, 9.1 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.84-4.30 (m, 1H), 4.57-4.52 (m, 2H), 1.60 (s, 6H) FA12 660.8 ([M + 2H]⁺) (300 MHz, DMSO-d₆) 3430, 1651, δ 9.87 (bs, 1H), 1261, 750 8.76 (bs, 1H), 7.98 (s, 1H), 7.95-7.91 (m, 3H), 7.83 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9, 1H), 4.89 (t, J = 9.6 Hz, 1H), 4.57-4.51 (m, 2H), 1.58 (s, 6H) FA13 606.8 ([M + H]⁺) (300 MHz, DMSO-d₆) 3418, 1651, δ 10.36 (s, 1H), 1164, 749 8.67 (bs, 1H), 8.56 (bs, 1H), 7.92 (s, 1H), 7.61-7.58 (m, 3H), 7.44 (d, J = 7.8 Hz, 1H), 6.96 (dd, J = 15.4, 8.8 Hz, 1H), 6.74 (d, J = 15.7 Hz, 1H), 4.61-4.70 (m, 1H), 4.04-3.90 (m, 4H) FA14 611.9 ([M + H]⁺) (400 MHz, CDCl₃) δ ¹⁹F NMR 7.69 (s, 1H), 7.62 (d, J = 1.6 Hz, (376 MHz, 1H), 7.53 (d, CDCl₃) δ- J = 8.0 Hz, 1H), 68.59 7.39 (m, 3H), 6.54 (d, J = 15.9 Hz, 1H), 6.40 (dd, J = 15.9, 7.8 Hz, 1H), 6.28 (s, 1H), 4.21 (d, J = 5.7 Hz, 2H), 4.12 (m, 1H), 1.69 (s, 6H) FA15 643.19 ([M + H]⁺) (400 MHz, CDCl3) δ ¹⁹F NMR 7.60 (d, J = 1.6 Hz, (376 MHz, 1H), 7.51 (d, J = 8.0 Hz, CDCl₃) δ- 1H), 7.40 (s, 2H), 68.62 7.36 (dd, J = 8.1, 1.6 Hz, 1H), 6.66 (d, J = 10.0 Hz, 2H), 6.53 (d, J = 15.9 Hz, 1H), 6.38 (dd, J = 15.9, 7.8 Hz, 1H), 4.11 (m, 1H), 3.12 (d, J = 6.2 Hz, 2H), 1.72 (s, 6H), 0.93 (s, 9H) FA16 687.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3433, 1640, δ 8.61-8.53 (m, 2H), 1163, 749 8.11 (s, 1H), 7.91 (s, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.74 (d, J = 15.9 Hz, 1H), 4.85-4.82 (m, 1H), 4.50-4.45 (m, 1H), 4.00-3.88 (m, 2H), 1.36 (d, J = 7.5 Hz, 3H) FA17 587.1 ([M + H]⁺) (300 MHz, DMSO-d₆) 3419, 1644, δ 8.60-8.53 (m, 2H), 1162, 748 7.91-7.85 (m, 3H), 7.54 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.02 (dd, J = 17.4, 11.1 Hz, 1H), 6.92 (dd, J = 15.9, 9.0 Hz, 1H), 6.81 (d, J = 15.9 Hz, 1H), 5.95 (d, J = 17.1 Hz, 1H), 5.33 (d, J = 11.7 Hz, 1H), 4.87-4.80 (m, 1H), 4.47-4.43 (m, 1H), 4.01-3.87 (m, 2H), 1.31 (d, J = 6.9 Hz, 3H) FA18 573.2 ([M + H]⁺) (300 MHz, DMSO-d₆) 3422, 1649, δ 8.62-8.56 (m, 2H), 1164, 809 7.91-7.86 (m, 3H), 7.56 (d, J = 9.3 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.11 (dd, J = 17.4, 11.1 Hz, 1H), 6.98 (dd, J = 15.9, 9.3 Hz, 1H), 6.82 (d, J = 15.9 Hz, 1H), 5.96 (d, J = 16.8 Hz, 1H), 5.34 (d, J = 12.0 Hz, 1H), 4.87-4.81 (m, 1H), 4.01-3.89 (m, 4H) FA19 667.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3288, 1645, δ 8.64-8.58 (m, 2H), 1164, 743, 7.92-7.89 (m, 3H), 563 7.60 (d, J = 8.1 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.3, 8.7 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.86-4.79 (m, 1H), 4.49-4.42 (m, 1H), 4.07-3.81 (m, 2H), 1.65-1.59 (m, 2H), 1.40-1.30 (m, 2H), 0.89 (t, J = 6.9 Hz, 3H) FA20 609.1 ([M + H]⁺) (400 MHz, DMSO-d₆) 3422, 2926, δ 8.74 (d J = 7.6 Hz, 1651, 1165, 1H), 8.59 (t, J = 6.4 Hz, 783 1H), 7.95 (s, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.72 (s, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.02 (dd, J = 16.0, 8.8 Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.76-4.72 (m, 1H), 4.51-4.47 (m, 1H), 3.99-3.88 (m, 2H), 2.42 (s, 3H), 1.29 (d, J = 7.2 Hz, 3H) FA21 673.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3429, 1650, δ 8.74 (d, J = 7.5 Hz, 1165, 804 1H), 8.59 (t, J = 6.3 Hz, 1H), 7.98 (s, 1H), 7.91-7.85 (m, 3H), 7.56 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.9, 9.3 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.81 (m, 1H), 4.52-4.57 (m, 1H), 4.04-3.85 (m, 2H), 1.29 (t, J = 6.9 Hz, 3H) FA22 681.0 ([M − H]⁻) (300 MHz, DMSO-d₆) 3298, 1651, δ 8.65 (d, J = 7.5 Hz, 1164, 689, 1H), 8.55 (t, J = 5.7 Hz, 536 1H), 7.91-7.85 (m, 2H), 7.48-7.39 (m, 2H), 7.31-7.26 (m, 1H), 7.00 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.86-4.82 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H) FA23 651.2 ([M + H]⁺) (400 MHz, CDCl₃) δ ¹⁹F NMR 7.61 (d, J = 1.6 Hz, (376 MHz, 1H), 7.51 (d, J = 8.0 Hz, CDCl₃) δ −68.61, 1H), 7.40 (s, 2H), −96.22 7.37 (dd, J = 8.1, 1.6 Hz, 1H), 6.85 (t, J = 6.2 Hz, 1H), 6.53 (d, J = 15.9 Hz, 1H), 6.42 (s, 1H), 6.38 (dd, J = 15.9, 7.8 Hz, 1H), 4.11 (m, 1H), 3.70 (td, J = 13.3, 6.3 Hz, 2H), 1.67 (m, 9H) FA24 672.9 ([M + H]⁺) (400 MHz, DMSO-d₆) 3410, 1653, δ 8.49 (t, J = 6.0 Hz, 1164, 812 1H), 8.42 (t, J = 6.4 Hz, 1H), 7.98 (s, 1H), 7.76 (s, 2H), 7.49-7.47 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.82 (dd, J = 15.6, 9.2 Hz, 1H), 6.59 (d, J = 16.4 Hz, 1H), 4.70-4.65 (m, 1H), 3.89-3.75 (m, 4H) FA25 603.0 ([M + H]⁺) (400 MHz, DMSO-d₆) 3288, 1676, δ 8.61 (t, J = 6.4 Hz, 1164, 809 1H), 8.37 (d, J = 8.0 Hz, 1H), 7.89 (s, 2H), 7.45 (s, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.86 (dd, J = 16.0, 8.8 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85-4.80 (m, 1H), 4.47-4.41 (m, 1H), 4.02-3.96 (m, 1H), 3.90-3.83 (m, 1H), 2.32 (s, 3H), 1.67-1.61 (m, 2H), 1.42-1.28 (m, 2H), 0.89 (t, J = 7.6 Hz, 3H) FA26 108-111 726.9 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 8.65 (d, J = 7.2 Hz, 1H), 8.55 (t, J = 6.3 Hz, 1H), 8.04 (s, 1H), 7.92 (s, 1H), 7.84-7.76 (m, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.01 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.84-4.78 (m, 1H), 4.51-4.46 (m, 1H), 4.00-3.88 (m, 2H), 1.31 (d, J = 7.5 Hz, 3H) FA27 103-107 717.1 ([M + H]⁺) (300 MHz, DMSO-d₆) δ 8.74 (d, J = 6.9 Hz, 1H), 8.59 (t, J = 6.0 Hz, 1H), 8.06 (s, 1H), 7.91-7.79 (m, 3H), 7.56 (d, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.9, 8.6 Hz, 1H), 6.88 (d, J = 15.3 Hz, 1H), 4.84-4.81 (m, 1H), 4.52-4.47 (m, 1H), 3.99-3.88 (m, 2H), 1.29 (d, J = 6.9 Hz, 3H) FA28 588.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3361, 2960, δ 8.59 (t, J = 6.6 Hz, 1690, 1166, 1H), 8.51 (d, J = 6.9 Hz, 819 1H), 7.88 (s, 2H), 7.22 (s, 2H), 6.75-6.63 (m, 2H), 4.83-4.77 (m, 1H), 4.50-4.49 (m, 1H), 4.00-3.87 (m, 2H), 2.21 (s, 6H), 1.33-1.22 (m, 3H) FA29 600.8 ([M + H]⁺) (400 MHz, DMSO-d₆) 3288, 1687, δ 8.63 (d, J = 7.2 Hz, 1164, 748, 1H), 8.55 (t, J = 6.4 Hz, 568 1H), 7.86 (s, 2H), 7.77 (d, J = 2.0 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.47 (dd, J = 10.0, 8.0 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 6.94 (dd, J = 15.6, 9.3 Hz, 1H), 6.63 (d, J = 15.6 Hz, 1H), 4.48-4.43 (m, 1H), 4.05-3.92 (m, 2H), 1.64 (t, J = 19.2 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H) FA30 655.0 ([M + H]⁺) (300 MHz, DMSO-d₆) 3418, 1717, δ 8.64 (d, J = 7.5 Hz, 1165, 748, 1H), 8.58 (t, J = 6.3 Hz, 525 1H), 7.95-7.91 (m, 2H), 7.66 (s, 2H), 7.60 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 6.99 (dd, J = 15.9, 9.3 Hz, 1H), 6.78 (d, J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.50-4.46 (m, 1H), 4.00-3.85 (m, 2H), 1.31 (d, J = 7.5 Hz, 3H) FA31 598.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3406, 1645, δ 8.65 (d, J = 7.5 Hz, 1163, 749, 1H), 8.55 (t, J = 5.7 Hz, 597 1H), 7.89 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.46 (s, 1H), 7.41 (d, J = 7.8 Hz, 2H), 7.31 (s, 1H), 6.96 (dd, J = 15.9, 8.7 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.71 (t, J = 9.3 Hz, 1H), 4.50 (t, J = 7.5 Hz, 1H), 4.00-3.88 (m, 2H), 2.67-2.60 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H), 1.21 (t, J = 7.5 Hz, 3H) FA32 666.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3288, 1645, δ 8.68 (s, 1H), 8.54 (d, 1165, 750 J = 8.4 Hz, 1H), 7.96-7.91 (m, 3H), 7.59 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 6.6 Hz, 1H), 6.98 (dd, J = 15.6, 8.0 Hz, 1H), 6.77 (d, J = 15.9, 1H), 4.88-4.72 (m, 1H), 4.36-4.31 (m, 1H), 4.07-3.81 (m, 2H), 2.06-1.99 (m, 1H), 0.95-0.85 (m, 6H) FA33 656.9 ([M + H]⁺) (300 MHz, DMSO-d₆) 3294, 1650, δ 8.71 (d, J = 6.3 Hz 1165, 810 1H), 8.65 (d, J = 8.4 Hz, 1H), 7.98 (s, 1H), 7.92-7.87 (m, 3H), 7.45 (d, J = 8.1 Hz, 1H), 7.03 (dd, J = 1 6 Hz, 8.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.88-4.82 (m, 1H), 4.35-4.10 (m, 1H), 4.07-3.81 (m, 2H), 2.06-1.99 (m, 1H), 0.95-0.85 (m, 6H) FA34 608.85 ([M + H]⁺) (300 MHz, DMSO-d₆) 768, 721, δ 9.01 (t, J = 6.0, 1H), 416, 337, 164 8.37 (t, J = 6.4 Hz, 1H), 8.08 (s, 1H), 8.01-7.96 (m, 1H), 7.88-7.86 (m, 2H), 7.64 (d, J = 7.6 Hz, 1H), 7.05 (dd, J = 16.4, 8.8 Hz, 1H), 6.91 (d, J = 15.6 Hz, 1H), 4.87-4.80 (m, 1H), 3.98-3.91 (m, 4H), 3.38 (s, 3H) ^(a) ¹H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 3 Assays Results Part 1 Compound BAW CEW GPA Number Rating Rating Rating AC1 D D B AC2 C C C AC3 D D B AC4 D A B AC5 D D B AC6 D A B AC7 A A B AC8 D B B AC9 A A B AC10 A A B AC11 A A D AC12 A A D AC13 A A B AC14 A B D AC15 A A B AC16 A A C AC17 A A B AC18 A A B AC19 D D B AC20 A A C AC21 D D C AC22 A A D AC23 A A B AC24 A A D AC25 A A D AC26 A A B AC27 A A B AC28 A A B AC29 A A B AC30 A A B AC31 A A B AC32 A A B AC33 A A B AC34 A A B AC35 A A C AC36 A A B AC37 A A B AC38 A A C AC39 A A C AC40 A A D AC41 A D D AC42 A D D AC43 A A B AC44 A A B AC45 A A D AC46 A A D AC47 D D B AC48 A A B AC49 A A B AC50 A D B AC51 A A B AC52 A A B AC53 A A B AC54 A A B AC57 A A B AC58 A A B AC59 A A B AC60 A A B AC61 A A B AC62 A A D AC63 A A B AC64 A A B AC65 A A B AC66 A A B AC67 A A B AC68 A A D AC69 A A A AC70 D D B AC71 A A B AC72 A A B AC75 A A B AC76 A A D AC77 A A B AC78 A A A AC79 A A A AC80 A A B AC81 A D D AC82 A A B AC83 A A B AC84 A A D AC85 A A B AC86 A A D AC87 A A B AC89 A A B AC90 A A C AC91 A A C AC92 A A C AC93 A D C AC94 D B B AC95 A A C AC96 D D C AC97 D D C AC98 A A C AC99 A A C AC100 C C C AC101 D D C AC102 D A C AC103 A A D AC104 A A B AC105 A A D AC106 A A B AC107 B A D AC108 B D D AC109 D D C AC110 A A C AC111 A A C AC112 A A C AC113 B A D AC114 A B D AC115 A A D AC116 C C C AC117 A D B AC118 A D D BC1 A A D BC2 A A D BC3 A A D BC4 A A B BC5 A A B BC6 A A D BC7 A A D BC8 A A B BC9 A A D BC10 A A B BC11 C C C BC12 C C C BC13 A A D BC14 A D D CC1 D D D CC2 A A B CC3 A A D CC4 A B B CC5 A A B CC6 A A B CC7 A A B CC8 A A D CC9 A A B CC10 A A B CC11 A A B CC12 D D B CC13 A A B CC14 A D D CC15 A A B CC16 A A B CC17 A A B CC18 A A B CC19 A A B CC20 A A D CC21 A A D CC22 A A B CC23 A A B CC24 A A D CC25 A A B CC26 A D B CC27 A A D CC28 A A D CC29 A A B CC30 A A D CC31 B D C CC32 A A B CC33 A A B CC34 A A B CC35 D D D CC36 A A D CC37 A A D CC38 A A D CC39 D D B CC40 D A D CC41 D D B CC42 D D D CC43 A B B CC44 A A B CC45 A A D CC46 D A C CC47 D D C CC48 D D C CC49 D D D CC50 A A D CC51 A A D CC52 A D D CC53 D D B CC54 A A C DC1 A A D DC2 D D C DC3 B D C DC4 A D C DC5 D D C DC6 D D C DC7 A D C DC8 A D C DC9 D D C DC10 D D C DC11 A D C DC12 A A B DC13 A A C DC14 D D C DC15 D D C DC16 A A C DC17 A A C DC18 A A C DC19 A A C DC20 A D C DC21 D D C DC22 D D C DC23 D A C DC24 D D C DC25 D D C DC26 D D C DC27 D D C DC28 A A B DC29 A A C DC30 A A C DC31 A A B DC32 D D C DC33 A A C DC34 A A B DC35 A A B DC36 D D C DC37 A A C DC38 A A C DC39 A A C DC40 A A C DC41 A A C DC42 A A C DC43 A A C DC44 A A C DC45 A A C DC46 A A C DC47 A A C DC48 A A C DC49 A A C DC50 A A C DC51 A A C DC52 D D C DC53 D A C DC54 D D C DC55 D D C DC56 D D C DC57 A A C DC58 D D C DC59 D D C DC60 A A C DC61 D D C DC62 A A C DC63 A A C DC64 D D C DC65 D A C DC66 A A C DC67 A A C DC68 A A C DC69 D D C DC70 A A C

TABLE 4 Assays Results F Compounds Compound BAW CL GPA Number Rating Rating Rating Fl A A B F2 A A C F3 A A C F4 A A C F5 A A C F6 C C C F7 A A C F8 A A C F8A A A C F9 A A C F10 A A C F11 A A C F12 A A C F13 A A C F14 A A C F15 A A C F15A A A C F16 A A C F16A A A C F17 A A C F18 A A C F19 A A C F20 A A C F20A A A A F20B A A C F20C A A C F21 A A C F22 A A C F23 D A C F23A A A C F24 A A C F25 A A C F26 A A C F27 A A C F28 A A C F29 A A C F30 A A C F31 A A C

TABLE 5 Assay Results Prophetic Compounds Subsequently Exemplified Compound BAW CL GPA Number Rating Rating Rating P1 A A C P2 D A C P12 A A C P14 B A C P15 A A C P82 A A C P84 A A C P156 A A C P226 A A C P228 A A C P298 D A B P300 A A C P442 A A C P444 A A C P514 A A C P516 A A C P568 A A C P586 A A C P588 A A C P660 A A C P730 A A C P732 A A C P802 A A C P804 A A C P1090 A A C P1092 A A C P1197 A A C P1269 A A C P1340 A A C P1411 A A B P1483 A A C P1556 A A C P1558 A A C P1559 A A C P1560 A A C P1564 A A C P1566 A A A P1589 A A C P1591 A A C P1592 A A C P1599 A A C P1601 A A B P1603 A A C P1611A A A C P1613A A A C P1616 A A C P1616A A A C P1618A A A C P1621 A A C P1623 A A C P1624 A A A P1631A A A B P1633A A A C P1636 A A C P1638 A A C P1640 D A D P1641 A A C P1691 A A C P1693 A A C P1696 A A C P1698 A A C P1776 A A C P1781 A A C P1806 A A C P1808 A A C P1862 A A C P1864 A A C P1866 A A C P1969* A A C P1970 A A C P1971 A A C P1972 A A C P2009 A A C P2010 A A C P2011 A A C P2012 A A C P2036 A A C P2038 A A C P2041 A A C P2043 A A C P2056 A A C P2058 A A C *Performed at 12.5 ug/cm²

TABLE 6 Assay Results FA Compounds Compound BAW CL GPA Number Rating Rating Rating FA1 A A C FA2 A A C FA3 A A C FA4 A A C FA5 A A C FA6 A A C FA7 A A C FA8 B A C FA9 A A C FA10 B B C FA11 B A D FA12 A A C FA13 D A C FA14 A A C FA15 A A C FA16 A A A FA17 A A C FA18 A A C FA19 A A C FA20 A A C FA21 A A C FA22 A A C FA23 A A C FA24 A A C FA25 A A C FA26 A A C FA27 A A C FA28 A A C FA29 A A C FA30 A A C FA31 A A C FA32 A A C FA33 A A C FA34 D A C 

We claim:
 1. A composition comprising a molecule according to Formula One:

wherein: (a) R1 is H; (b) R2 is H, F, Cl, Br, I, or (C₁-C₈)alkyl; (c) R3 is F, Cl, Br, I, (C₁-C₈)alkoxy, or halo(C₁-C₈)alkoxy; (d) R4 is F, Cl, Br, I, or (C₁-C₈)alkyl; (e) R5 is H; (f) R6 is (C₁-C₈)haloalkyl; (g) R7 is H; (h) R8 is H; (i) R9 is H; (j) R10 is F, Cl, Br, I, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, S(O)₂(C₁-C₈)alkyl, NR14R15, or (C₂-C₈)alkenyl; (k) R11 is selected from C(═X5)N(R14)((C₁-C₈)alkylC(═X5)N(R14)(R15)) wherein each X5 is independently selected from O, or S; (l) R12 is H, or (C₁-C₈)alkyl; (m) R13 is H, or (C₁-C₈)alkoxy; (n) R14 is H; (o)R15 is H; (r) X1 is CR12; (s) X2 is CR13; and (t) X3 is CR9.
 2. A molecule according to claim 1 wherein R11 is selected from C(═O)N(H)(C((CH₃)₂)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₂CH₃)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═S)N(H)(CH₂CF₃)), C(═O)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)), and C(═S)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)).
 3. A molecule according to claim 1 wherein R11 is C(═(O or S))N(H)(((C₁-C₈)alkyl)C(═(O or S))N(H)(halo(C₁-C₈)alkyl)).
 4. A molecule according to claim 1 wherein R11 is selected from C(═O)N(H)(C((CH₃)₂)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═O)N(H)(CH₂CF₃)), C(═O)N(H)(CH(CH₃)C(═S)N(H)(CH₂CF₃)), C(═O)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)), and C(═S)N(H)(C((CH₃)₂)C(═S)N(H)(CH₂CF₃)).
 5. A molecule according to claim 1 wherein R11 is selected from C(═O)N(H)(C((CH₃)₂)C(═O)N(H)(CH₂CF₃)).
 6. A composition according to claim 1 further comprising: (a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties; or (b) one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists; or (c) both (a) and (b).
 7. A composition according to claim 1 wherein further comprising one or more compounds selected from: (3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-5-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlomidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DB CP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl, fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluoron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluoron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid.
 8. A composition according to claim 1 further comprising an agriculturally acceptable carrier.
 9. A composition according to claim 1 wherein said molecule is in the form of a pesticidally acceptable acid addition salt.
 10. A composition according to claim 1 wherein said molecule is in the form of a salt derivative.
 11. A composition according to claim 1 wherein said molecule is in the form a hydrate.
 12. A composition according to claim 1 wherein said molecule is in the form an ester derivative.
 13. A composition according to claim 1 wherein said molecule is in the form a crystal polymorph.
 14. A composition according to claim 1 wherein said molecule has a ²H in place of ¹H.
 15. A composition according to claim 1 wherein said molecule has a ¹⁴C in place of a ¹²C.
 17. A composition according to claim 1 further comprising a biopesticide.
 17. A composition according to claim 1 further comprising one or more of the following compounds: (a) 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; (b) 3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; (c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; (d) 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; (e) 3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide; (f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; (g) 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h) 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; (i) 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; (j) 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; (k) 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (l) 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; (m) 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide; (n) N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone; (o) N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl) hydrazone nicotine; (p) O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methyl thiocarbonate; (q) (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine; (r) 1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol; (s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and (t) N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.
 18. A composition according to claim 1 further comprising a compound having one or more of the following modes of action: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).
 19. A composition according to claim 1 further comprising a seed.
 20. A composition according to claim 1 further comprising a seed that has been genetically modified to express one or more specialized traits.
 21. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule.
 22. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule, wherein said capsule has a diameter of about 100-900 nanometers or about 10-900 microns.
 23. A process comprising applying a composition according to claim 1, to an area to control a pest, in an amount sufficient to control such pest.
 24. A process according to claim 23 wherein said pest is selected from beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
 25. A process according to claim 23 wherein said pest is from the Phyla Nematoda or Arthropoda.
 26. A process according to claim 23 wherein said pest is from the Subphyla Chelicerata, Myriapoda, or Hexapoda.
 27. A process according to claim 23 wherein said pest is from the Class of Arachnida, Symphyla, or Insecta.
 28. A process according to claim 23 wherein said pest is from the Order Anoplura, Order Coleoptera, Order Dermaptera, Order Blattaria, Order Diptera, Order Hemiptera, Order Hymenoptera, Order Isoptera, Order Lepidoptera, Order Mallophaga, Order Orthoptera, Order Siphonaptera, Order Thysanoptera, Order Thysanura, Order Acarina, or Order Symphyla.
 29. A process according to claim 23 wherein said pest is BAW, CEW, or GPA.
 30. A process according to claim 23 wherein said amount is from about 0.01 grams per hectare to about 5000 grams per hectare.
 31. A process according to claim 23 wherein said amount is from about 0.1 grams per hectare to about 500 grams per hectare.
 32. A process according to claim 23 wherein said amount is from about 1 gram per hectare to about 50 grams per hectare.
 33. A process according to claim 23 wherein said area is an area where apples, corn, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted.
 34. A process according to claim 23 further comprising applying said composition to a genetically modified plant that has been genetically modified to express one or more specialized traits.
 35. A process according to claim 1 where said composition further comprise ammonium sulfate.
 36. A process comprising: orally administering; or topically applying; a composition according to claim 1, to a non-human animal, to control endoparasites, ectoparasites, or both.
 37. A process comprising applying a composition according to claim 1 to a plant to enhance the plant's health, yield, vigor, quality, or tolerance, at a time when pest activity is low. 